Self-assembling peptides and hydrogels

Abstract

The present invention relates peptides capable of forming a hydrogel by self-assembly, wherein the peptide consists of 6 to 12 amino acids and containing the amino acid sequence X1–A4–A5–A6–X2. Said peptides self-assemble especially under mild conditions in an aqueous dispersion phase thereby forming a hydrogel and are thus particularly useful for forming a hydrogel composition.

Description

[0001] Self-assembling peptides and hydrogels

[0002] Specification

[0003] Field of the invention

[0004] The present invention relates to peptides capable of forming a hydrogel by selfassembly, wherein the peptide consists of 6 to 12 amino acids and containing the amino acid sequence X1-A4-A5-A6-X2. Said peptides self-assemble especially under mild conditions in an aqueous dispersion phase thereby forming a hydrogel and are thus particularly useful for forming a hydrogel composition.

[0005] Background of the invention

[0006] Hydrogels are three-dimensional polymeric networks capable of retaining large amounts of water, making them highly versatile materials for various biomedical and industrial applications. Due to their special properties, hydrogels are used in many areas, including drug delivery systems, tissue engineering, wound healing, contact lenses, biosensors, agriculture, 3D bioprinting, hygiene products, and food supplements.

[0007] U.S. patent US 7 862 826 B2 is related to antimicrobial peptide compositions and methods for treating injuries to the nervous system of animals. Antimicrobial peptides such as lysozyme C act as antimicrobial agents and promoters of cell survival, differentiation, and tissue regeneration. Trophic factors support neuron growth, survival, and functional recovery.

[0008] Hamodrakas et al. (Int. J. Biolog. Macromol. 2007, 41 (3), 295-300) report on a consensus approach to predict amyloidogenic determinants in protein sequences by integrating three computational methods, two algorithms predicting amyloidogenic stretches based on sequence features and one secondary structure predictor identifying conformational switches (regions prone to switch between a-helix and [3-sheet structures). The in silico study analyzed 21 known amyloid-forming proteins and identified short amino acid sequences with a high propensity for self-assembly.

[0009] US 2022 / 267373 A1 discloses self-assembling pentapeptides and peptides containing such pentapeptides. The synthetic pentapeptides are minimalist, artificial constructs optimized through sequence engineering for specific rheological behavior to form hydrogels under physiological conditions. The pentapeptides are thus useful

[0010] GAR-P04562WO16 Application (final) docx for tissue engineering scaffolds, 2D / 3D cell culture systems, drug delivery and encapsulation, injectables and in s / fu-gelling systems (e.g., hemostatics), wound care, transplantation, and virus culture / storage.

[0011] Among the different classes of hydrogels, peptide-based hydrogels have garnered significant attention due to their biocompatibility, tunable properties, and ability to self-assemble under physiological conditions. Peptides, as building blocks, offer unique advantages, such as molecular recognition, biodegradability, and the ability to form specific secondary structures, which can be leveraged to create hydrogels with tailored mechanical and chemical characteristics. However, the production of peptide hydrogels can be costly and complex, particularly for large-scale applications, due to the need for precise peptide synthesis and purification techniques.

[0012] Therefore, it is the objective of the present invention to provide a novel class of peptide hydrogels with versatile mechanical properties that can be tailored to various uses in diverse fields.

[0013] The objective of the present invention is solved by the teaching of the independent claims. Further advantageous features, aspects and details of the invention are evident from the dependent claims, the description, the figures, and the examples of the present application.

[0014] Brief description of the invention

[0015] The present invention is directed to a peptide capable of forming a hydrogel by selfassembly, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I):

[0016] X1-A4-A5-A6-X2(I) wherein

[0017] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0018] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0019] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0020] -A7-A8-A9-A10-A11;

[0021] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0022] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0023] GAR-P04562WO16 Application (final) docx A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0024] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0025] A7and A8represent independently of each other a neutral amino acid;

[0026] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0027] A10represents a basic amino acid, or an aromatic amino acid;

[0028] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0029] As used in the definitons herein, “-H” designates the free amino terminus (NH2group) of the peptide and is not an abbreviation for histidine. The symbol “C” denotes the amino acid cysteine, not a carbon atom. Thus, the expession » X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or C-A1-A2-A3-; « is to be understood as » X1represents the amino terminus (-H), a cysteine residue (C-), A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or C-A1-A2-A3-“ «, wherein C denotes the amino acid cysteine and “-H” denotes the free N-terminal hydrogen.

[0030] The inventors have surprisingly found that the inventive short peptides of the sequence X1-A4-A5-A6-X2form hydrogels through self-assembly into peptide aggregates or formation of networks. Using rheology experiments and TEM imaging, the inventors examined the influence of sequence variations, pH, and peptide concentration on the mechanical properties of the herein disclosed hydrogels. The experimental data demonstrate that the inventive peptides form robust hydrogels (e.g. from about 10 to about 100,000 Pa storage modulus) at low weight percent.

[0031] Two key parameters are of particular significance for the comprehensive understanding of the material viscoelastic properties as they provide insights into stiffness and damping characteristics: i) Storage Modulus (G’)= Measure of the stored energy in a material during deformation and reflection of the material’s elastic behavior. Indication of the amount of energy a material can store when subjected to a deforming force and subsequently release when the force is removed. A higher storage modulus indicates higher stiffness and lower deformability of the material. ii) Loss Modulus (G”): Measure of the dissipated energy, e.g., as heat during deformation and reflection of the material’s viscous behavior. Indication of the amount of energy a material loses when subjected to a deforming force. A higher loss modulus indicates more damping and energy dissipation by the material.

[0032] GAR-P04562WO16 Application (final) docx In the field of self-assembling peptides and peptide-based hydrogels, prior art documents such as Hamodrakas et al. (Int. J. Biolog. Macromol. 2007, 41 (3), 295- and patent application US 2022 / 267373 A1 illustrate distinct but limited approaches. Patent application US 2022 / 267373 A1 discloses short, synthetic pentapeptides rationally designed to form hydrogels under physiological conditions. These peptides are minimalist, artificial constructs optimized through sequence engineering for specific rheological behavior. The design rationale of US 2022 / 267373 A1 , which focuses on constructing de novo pentapeptides, is fundamentally different from the present invention, which is based on biologically inspired sequences derived from natural Lysozyme C. Consequently, US 2022 / 267373 A1 addresses a different technical problem, namely, the engineering of minimal synthetic self-assembling sequences, whereas the present invention provides modular peptides containing naturally occurring motifs that exhibit self-assembly and gelation, thereby bridging the gap between biological structure and synthetic functionality.

[0033] In contrast, Hamodrakas et al. identify short peptide fragments within lysozyme, including GISLAN (SEQ ID NO: 3) and SLANWMCL (SEQ ID NO: 1273), as potential amyloidogenic or conformational switching regions. These conclusions are based exclusively on computational predictions and relate to local structural packing within the folded protein. Hamodrakas et al. do not disclose or suggest any hydrogel formation, nor do they provide experimental evidence that such short motifs, when isolated, can self-assemble into amyloids, (functional) peptide nanofibrils or macroscopic, hydrated networks. The density of molecular packing observed in amyloid structures cannot be directly equated with hydrogel formation. Amyloid formation and hydrogel formation represent fundamentally different processes. Amyloid fibrils result from highly ordered [3-sheet stacking and lateral association of peptide strands, which often produces rigid, densely packed and often crystalline aggregates. Such aggregates typically precipitate from solution, forming insoluble deposits rather than extended, hydrated networks. In contrast, hydrogel formation requires the development of a three-dimensional network that can immobilize large amounts of water while maintaining macroscopic integrity.

[0034] In most cases, amyloidogenic sequences lack the long-range, dynamic intermolecular interactions necessary to establish such network connectivity. Their strong [3-sheet interactions drive phase separation and aggregate nucleation, leading to fibril bundles or amorphous precipitates instead of continuous gels. These assemblies are often irreversible and brittle, and they do not exhibit the viscoelastic

[0035] GAR-P04562WO16 Application (final) docx or reversible shear-thinning behavior characteristic of the herein reported peptide hydrogels.

[0036] While some short amyloidogenic sequences have been reported to form weak or conditional gels at high concentration, such behavior is not predictive of general gelation capability. For example, the KLVFF (SEQ ID NO: 1274) fragment from the amyloid-[3 peptide (AP16-20), predominantly forms fibrillar aggregates, and produces only fragile, reversible gels under specific conditions (see Krysmann et al., Biochemistry 2008, 47, 4597-4605). Other well-known amyloidogenic motifs, such as NNQQNY (SEQ ID NO: 1275) from the yeast prion Sup35 and STVIIE (SEQ ID NO: 1276) from transthyretin, also assemble into dense [3-sheet fibrils but do not yield macroscopic hydrogels.

[0037] Accordingly, the mere identification of an amyloidogenic or conformationally switching region, such as GISLAN (SEQ ID NO: 3) in Hamodrakas et al., does not imply or suggest hydrogel formation. The ability to form hydrogels depends on a delicate balance between local peptide-peptide interactions and long-range cooperative associations that allow partial solvation and network percolation. This emergent property is not predictable from amyloidogenicity alone and requires targeted sequence design and experimental validation, as achieved in the present invention.

[0038] The invention resides in the identification, synthesis, and experimental validation of specific peptides of general formula (I) that exhibit reproducible hydrogel formation and self-assembly in aqueous media.

[0039] Reworded, the present invention is directed to a peptide capable of forming a hydrogel by self-assembly, wherein the peptide consists of 6 to 12 amino acids and having the amino acid sequence of general formula (I), and wherein X1, X2, A4, A5, and A6have the meanings as defined herein

[0040] In other words, the present invention is directed to a peptide capable of selfassembling and hydrogel formation, wherein the peptide consists of 6 to 12 amino acids and having the amino acid sequence of general formula (I), and wherein X1, X2, A4, A5, and A6have the meanings as defined herein.

[0041] In a prefrerred embodiment, the self-assembling peptide consists of at least 6 amino acids having the following amino acid sequence of general formula (I):

[0042] GAR-P04562WO16 Application (final) docx X1-A4-A5-A6-X2(I) wherein

[0043] X1represents -H, A3-, A2-A3-, or A1-A2-A3-;

[0044] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0045] -A7-A8-A9-A10-A11;

[0046] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0047] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0048] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0049] A6represents an amino acid selected from S, and T;

[0050] A7and A8represent independently of each other a neutral amino acid;

[0051] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0052] A10represents a basic amino acid, or an aromatic amino acid;

[0053] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0054] As used herein, the expression “the self-assembling peptide consists of at least six amino acids having the following amino acid sequence of general formula (I)” is to be understood by the skilled person as defining a peptide whose sequence follows the pattern of formula (I) and has a minimum length of six amino acids. The term “at least” merely specifies this lower limit and does not imply that the peptide may have an arbitrary or unlimited length. In the context of the disclosure, including the examples and the definition of X1and X2, the skilled person recognises that the total length of the peptide is limited by the maximum extension defined in formula (I), i.e. typically up to eleven amino acids. Accordingly, the claim does not encompass peptides longer than those covered by the structural variants described in formula (I).

[0055] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0056] X1-A4-A5-A6-X2(I) wherein

[0057] GAR-P04562WO16 Application (final) docx X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0058] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0059] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0060] -A7-A8-A9-A10-A11;

[0061] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0062] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0063] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0064] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0065] A7and A8represent independently of each other a neutral amino acid;

[0066] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0067] A10represents a basic amino acid, or an aromatic amino acid;

[0068] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide, with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0069] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0070] X1-A4-A5-A6-X2(I) wherein

[0071] X1represents -H, A3-, A2-A3- , or A1-A2-A3-,

[0072] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0073] -A7-A8-A9-A10-A11;

[0074] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0075] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0076] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0077] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0078] A7and A8represent independently of each other a neutral amino acid;

[0079] GAR-P04562WO16 Application (final) docx A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0080] A10represents a basic amino acid, or an aromatic amino acid;

[0081] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide, with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0082] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0083] X1-A4-A5-A6-X2(I) wherein

[0084] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0085] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0086] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0087] -A7-A8-A9-A10-A11;

[0088] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0089] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0090] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0091] A6represents an amino acid selected from S, T, C, N, Q, Y, A, and G;

[0092] A7and A8represent independently of each other a neutral amino acid;

[0093] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0094] A10represents a basic amino acid, or an aromatic amino acid;

[0095] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0096] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0097] X1-A4-A5-A6-X2(I)

[0098] GAR-P04562WO16 Application (final) docx wherein

[0099] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0100] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0101] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0102] -A7-A8-A9-A10-A11;

[0103] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0104] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0105] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0106] A6represents an amino acid selected from S, T, C, N, Q, and Y;

[0107] A7and A8represent independently of each other a neutral amino acid;

[0108] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0109] A10represents a basic amino acid, or an aromatic amino acid;

[0110] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0111] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0112] X1-A4-A5-A6-X2(I) wherein

[0113] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0114] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0115] -A7-A8-A9-A10-A11;

[0116] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0117] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0118] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0119] A6represents an amino acid selected from S, T, C, N, Q, and Y;

[0120] A7and A8represent independently of each other a neutral amino acid;

[0121] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0122] GAR-P04562WO16 Application (final) docx ABK "

[0123] 10

[0124] A10represents a basic amino acid, or an aromatic amino acid;

[0125] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0126] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0127] X1-A4-A5-A6-X2(I) wherein

[0128] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0129] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0130] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0131] -A7-A8-A9-A10-A11;

[0132] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0133] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0134] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0135] A6represents an amino acid selected from S, T, C, N, and Q;

[0136] A7and A8represent independently of each other a neutral amino acid;

[0137] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0138] A10represents a basic amino acid, or an aromatic amino acid;

[0139] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0140] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0141] X1-A4-A5-A6-X2(I) wherein

[0142] X1represents ■ H, A3-, A2-A3- , or A1-A2-A3-

[0143] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10A11;

[0144] GAR-P04562WO16 Application (final) docx A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0145] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0146] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0147] A6represents an amino acid selected from S, T, C, N, and Q;

[0148] A7and A8represent independently of each other a neutral amino acid;

[0149] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0150] A10represents a basic amino acid, or an aromatic amino acid;

[0151] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0152] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0153] X1-A4-A5-A6-X2(I) wherein

[0154] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0155] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0156] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0157] -A7-A8-A9-A10-A11;

[0158] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0159] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0160] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0161] A6represents an amino acid selected from S, T, C, N, and Y;

[0162] A7and A8represent independently of each other a neutral amino acid;

[0163] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0164] A10represents a basic amino acid, or an aromatic amino acid;

[0165] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0166] GAR-P04562WO16 Application (final) docx -=ABK

[0167] 12

[0168] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0169] X1-A4-A5-A6-X2(I) wherein

[0170] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0171] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0172] -A7-A8-A9-A10-A11;

[0173] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0174] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0175] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0176] A6represents an amino acid selected from S, T, C, N, and Y;

[0177] A7and A8represent independently of each other a neutral amino acid;

[0178] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0179] A10represents a basic amino acid, or an aromatic amino acid;

[0180] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0181] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0182] X1-A4-A5-A6-X2(I) wherein

[0183] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0184] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0185] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0186] -A7-A8-A9-A10-A11;

[0187] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0188] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0189] GAR-P04562WO16 Application (final) docx -=ABK

[0190] 13

[0191] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0192] A6represents an amino acid selected from S, T, C, N, and Y;

[0193] A7and A8represent independently of each other a neutral amino acid;

[0194] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0195] A10represents a basic amino acid, or an aromatic amino acid;

[0196] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide, with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0197] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0198] X1-A4-A5-A6-X2(I) wherein

[0199] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0200] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0201] -A7-A8-A9-A10-A11;

[0202] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0203] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0204] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0205] A6represents an amino acid selected from S, T, C, N, and Y;

[0206] A7and A8represent independently of each other a neutral amino acid;

[0207] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0208] A10represents a basic amino acid, or an aromatic amino acid;

[0209] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide, with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0210] GAR-P04562WO16 Application (final) docx -=ABK

[0211] 14

[0212] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0213] X1-A4-A5-A6-X2(I) wherein

[0214] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0215] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0216] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0217] -A7-A8-A9-A10-A11;

[0218] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0219] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0220] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0221] A6represents an amino acid selected from S, T, C, and N;

[0222] A7and A8represent independently of each other a neutral amino acid;

[0223] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0224] A10represents a basic amino acid, or an aromatic amino acid;

[0225] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0226] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0227] X1-A4-A5-A6-X2(I) wherein

[0228] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0229] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0230] -A7-A8-A9-A10-A11;

[0231] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0232] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0233] GAR-P04562WO16 Application (final) docx A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0234] A6represents an amino acid selected from S, T, C, and N;

[0235] A7and A8represent independently of each other a neutral amino acid;

[0236] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0237] A10represents a basic amino acid, or an aromatic amino acid;

[0238] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0239] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0240] X1-A4-A5-A6-X2(I) wherein

[0241] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0242] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0243] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0244] -A7-A8-A9-A10-A11;

[0245] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0246] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0247] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0248] A6represents an amino acid selected from S, T, and C;

[0249] A7and A8represent independently of each other a neutral amino acid;

[0250] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0251] A10represents a basic amino acid, or an aromatic amino acid;

[0252] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0253] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0254] GAR-P04562WO16 Application (final) docx X1-A4-A5-A6-X2(I) wherein

[0255] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0256] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0257] -A7-A8-A9-A10-A11;

[0258] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0259] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0260] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0261] A6represents an amino acid selected from S, T, and C;

[0262] A7and A8represent independently of each other a neutral amino acid;

[0263] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0264] A10represents a basic amino acid, or an aromatic amino acid;

[0265] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0266] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0267] X1-A4-A5-A6-X2(I) wherein

[0268] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0269] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0270] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0271] -A7-A8-A9-A10-A11;

[0272] A1represents an amino acid selected from G and A;

[0273] A2represents an amino acid selected from Y, F, and W;

[0274] A3represents an amino acid selected from R, K and L;

[0275] A4represents an amino acid selected from G, and A;

[0276] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0277] A6represents an amino acid selected from S, T, C, N, and Y;

[0278] A7represents an amino acid selected from L, I, and V;

[0279] A8represents an amino acid selected from A, G, and V;

[0280] GAR-P04562WO16 Application (final) docx A9represents an amino acid selected from K, N, and Q;

[0281] A10represents an amino acid selected from W, and F;

[0282] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G.

[0283] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0284] X1-A4-A5-A6-X2(I) wherein

[0285] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0286] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0287] -A7-A8-A9-A10-A11;

[0288] A1represents an amino acid selected from G and A;

[0289] A2represents an amino acid selected from Y, F, and W;

[0290] A3represents an amino acid selected from R, K and L;

[0291] A4represents an amino acid selected from G, and A;

[0292] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0293] A6represents an amino acid selected from S, T, C, N, and Y;

[0294] A7represents an amino acid selected from L, I, and V;

[0295] A8represents an amino acid selected from A, G, and V;

[0296] A9represents an amino acid selected from K, N, and Q;

[0297] A10represents an amino acid selected from W, and F;

[0298] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G.

[0299] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0300] X1-A4-A5-A6-X2(I) wherein

[0301] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0302] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0303] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0304] -A7-A8-A9-A10-A11;

[0305] A1represents an amino acid selected from G and A;

[0306] A2represents an amino acid selected from Y, F, and W;

[0307] GAR-P04562WO16 Application (final) docx A3represents an amino acid selected from R, K and L;

[0308] A4represents an amino acid selected from G, and A;

[0309] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0310] A6represents an amino acid selected from S, and T;

[0311] A7represents an amino acid selected from L, I, and V;

[0312] A8represents an amino acid selected from A, G, and V;

[0313] A9represents an amino acid selected from K, N, and Q;

[0314] A10represents an amino acid selected from W, and F;

[0315] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G.

[0316] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0317] X1-A4-A5-A6-X2(I) wherein

[0318] X1represents -H, A3-, A2-A3- , or A1-A2-A3-, ;

[0319] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0320] -A7-A8-A9-A10-A11;

[0321] A1represents an amino acid selected from G and A;

[0322] A2represents an amino acid selected from Y, F, and W;

[0323] A3represents an amino acid selected from R, K and L;

[0324] A4represents an amino acid selected from G, and A;

[0325] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0326] A6represents an amino acid selected from S, and T;

[0327] A7represents an amino acid selected from L, I, and V;

[0328] A8represents an amino acid selected from A, G, and V;

[0329] A9represents an amino acid selected from K, N, and Q;

[0330] A10represents an amino acid selected from W, and F;

[0331] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G.

[0332] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0333] X1-A4-A5-A6-X2(I) wherein

[0334] GAR-P04562WO16 Application (final) docx ABK "

[0335] 19

[0336] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0337] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0338] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0339] -A7-A8-A9-A10-A11;

[0340] A1represents an amino acid selected from G and A;

[0341] A2represents an amino acid selected from Y, F, and W;

[0342] A3represents an amino acid selected from R, K and L;

[0343] A4represents an amino acid selected from G, and A;

[0344] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0345] A6represents an amino acid selected from S, and T;

[0346] A7represents an amino acid selected from L, I, and V;

[0347] A8represents an amino acid selected from A, G, and V;

[0348] A9represents an amino acid selected from K, N, and Q;

[0349] A10represents an amino acid selected from W, and F;

[0350] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0351] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0352] X1-A4-A5-A6-X2(I) wherein

[0353] X1represents -H, A3-, A2-A3- , or A1-A2-A3-;

[0354] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0355] -A7-A8-A9-A10-A11;

[0356] A1represents an amino acid selected from G and A;

[0357] A2represents an amino acid selected from Y, F, and W;

[0358] A3represents an amino acid selected from R, K and L;

[0359] A4represents an amino acid selected from G, and A;

[0360] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0361] A6represents an amino acid selected from S, and T;

[0362] A7represents an amino acid selected from L, I, and V;

[0363] A8represents an amino acid selected from A, G, and V;

[0364] A9represents an amino acid selected from K, N, and Q;

[0365] A10represents an amino acid selected from W, and F;

[0366] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G

[0367] GAR-P04562WO16 Application (final) docx -=ABK

[0368] 20 with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0369] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0370] X1-A4-A5-A6-X2(I) wherein

[0371] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0372] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0373] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0374] -A7-A8-A9-A10-A11;

[0375] A1represents G;

[0376] A2represents an amino acid selected from Y, and F;

[0377] A3represents an amino acid selected from R, K and L;

[0378] A4represents G;

[0379] A5represents an amino acid selected from I, and Y;

[0380] A6represents an amino acid selected from S T, C, N, and Y;

[0381] A7represents L;

[0382] A8represents A;

[0383] A9represents an amino acid selected from K and N;

[0384] A10represents W;

[0385] A11represents an amino acid selected from M, M-NH2, and V.

[0386] In a preferred embodiment, the peptide capable of forming a hydrogel by selfassembly consists of 6 to 11 amino acids having the following amino acid sequence of general formula (I):

[0387] X1-A4-A5-A6-X2(I) wherein

[0388] X1represents -H, A3-, A2-A3- , or A1-A2-A3-,;

[0389] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0390] -A7-A8-A9-A10-A11;

[0391] A1represents G;

[0392] A2represents an amino acid selected from Y, and F;

[0393] A3represents an amino acid selected from R, K and L;

[0394] GAR-P04562WO16 Application (final) docx A4represents G;

[0395] A5represents an amino acid selected from I, and Y;

[0396] A6represents an amino acid selected from S T, C, N, and Y;

[0397] A7represents L;

[0398] A8represents A;

[0399] A9represents an amino acid selected from K and N;

[0400] A10represents W;

[0401] A11represents an amino acid selected from M, M-NH2, and V.

[0402] In another embodiment, thepeptide capable of forming a hydrogel by self-assembly consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I):

[0403] X1-A4-A5-A6-X2(I) wherein

[0404] X1represents A1-A2-A3- or A2-A3- ;

[0405] X2represents -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11;

[0406] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0407] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0408] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0409] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0410] A7and A8represent independently of each other a neutral amino acid;

[0411] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0412] A10represents a basic amino acid, or an aromatic amino acid;

[0413] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0414] In another embodiment, thepeptide capable of forming a hydrogel by self-assembly consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I):

[0415] X1-A4-A5-A6-X2(I) wherein

[0416] GAR-P04562WO16 Application (final) docx X1represents C-A1-A2-A3- , A1-A2-A3- , C-A2-A3- , or A2-A3- ; wherein C represents the amino acid cysteine;

[0417] X2represents -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11;

[0418] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0419] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0420] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0421] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0422] A7and A8represent independently of each other a neutral amino acid;

[0423] A9represents independently of each other a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0424] A10represents a basic amino acid, or an aromatic amino acid;

[0425] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

[0426] In a further preferred embodiment, the peptide capable of forming a hydrogel by selfassembly according to the invention consists of the amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GYKGISLANWM (SEQ ID NO: 7), GYRGISLANWM (SEQ ID NO: 8),

[0427] GYRGYSLANWM (SEQ ID NO: 9), GYRGITLANWM (SEQ ID NO: 10), GYRGISLAKWM (SEQ ID NO: 11 ) GYRGISLANWV (SEQ ID NO: 12),

[0428] GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2(SEQ ID NO: 14), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261 ), C GYRGITLANWM (SEQ ID NO: 1262), CYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264),

[0429] CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266),

[0430] CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268),

[0431] CGYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270),

[0432] CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

[0433] In a further preferred embodiment, the peptide capable of forming a hydrogel by selfassembly according to the invention consists of the amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GYKGISLANWM (SEQ ID NO: 7), GYRGISLANWM (SEQ ID NO: 8), GYRGYSLANWM (SEQ ID NO: 9),

[0434] GAR-P04562WO16 Application (final) docx GYRGITLANWM (SEQ ID NO: 10), GYRGISLAKWM (SEQ ID NO: 11 ) GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261 ), CGYRGITLANWM (SEQ ID NO: 1262), GYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264), CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266), CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268), CGYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270), CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

[0435] In a further preferred embodiment, the peptide capable of forming a hydrogel by selfassembly according to the invention consists of the amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GYKGISLANWM (SEQ ID NO: 7), GYRGISLANWM (SEQ ID NO: 8), GYRGYSLANWM (SEQ ID NO: 9), GYRGITLANWM (SEQ ID NO: 10), GYRGISLAKWM (SEQ ID NO: 11 ) GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14).

[0436] In a further preferred embodiment, the peptide capable of forming a hydrogel by selfassembly according to the invention consists of the amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GYKGISLANWM (SEQ ID NO: 7), GYRGISLANWM (SEQ ID NO: 8), GYRGYSLANWM (SEQ ID NO: 9), GYRGITLANWM (SEQ ID NO: 10), GYRGISLAKWM (SEQ ID NO: 11 ) GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), and GYRGISLANWM-NH2 (SEQ ID NO: 14).

[0437] In a further preferred embodiment, the peptide capable of forming a hydrogel by selfassembly according to the invention has the amino acid sequence GYRGISLANWM (SEQ ID NO: 8).

[0438] In a further embodiment, the peptide is capable of forming a hydrogel by selfassembly in an aqueous medium, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I), and wherein X1, X2, A4, A5, and A6have the meanings as defined herein.

[0439] In a further embodiment, the peptide is capable of forming a hydrogel by selfassembly in an aqueous medium, wherein the peptide consists of 6 to 12 amino

[0440] GAR-P04562WO16 Application (final) docx acids and having the following amino acid sequence of general formula (I), wherein X1, X2, A4, A5, and A6have the meanings as defined herein, and wherein the peptide is present in said aqueous medium at a level of from about 0.01 % by weight to about 20%, preferably from about 0.01% by weight to about 10% by weight, based upon the total weight of the medium.

[0441] In a further embodiment, the peptide is capable of forming a hydrogel by selfassembly in an aqueous medium, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I), wherein X1, X2, A4, A5, and A6have the meanings as defined herein, and wherein the peptide is present in said aqueous medium at a level of from about 0.01 % by weight to about 20%, preferably from about 0.01% by weight to about 10% by weight, based upon the total weight of the medium.

[0442] In a further embodiment, the peptide is capable of forming a hydrogel by selfassembly in an aqueous medium, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I), wherein X1, X2, A4, A5, and A6have the meanings as defined herein, and wherein hydrogel formation occurs at peptide concentrations of 8 wt% or less, preferably 6 wt% or less, more preferably 5 wt% or less, even more preferably 4 wt% or less, more preferably 3 wt % or less, preferably 2 wt % or less, preferably 1 wt % or less.

[0443] Preferably, the aqueous medium comprises one or more salts selected from (NH4)2SO4, Na2SO4, NaCI, KCI, CH3COONH4, NH3C(CH2OH)3CI, KH2PO4, and Na2HPO4.

[0444] The following buffers are preferred: acetate buffer, ammonium buffer (NH31 NH4+), Tris-HCI buffer, NH2C(CH2OH)3 / NH3+C(CH2OH)3buffer, TAE buffer, phosphate buffer, and phosphate buffered saline.

[0445] In a further embodiment, the peptide is capable of forming a hydrogel by selfassembly in an aqueous medium, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I), wherein X1, X2, A4, A5, and A6have the meanings as defined herein, and wherein the aqueous medium has a pH value between 4.0 and 9.0, preferably between 4.5 and 8.5, more preferably between 4.8 and 8.0, still more preferably between 5.0 and 7.5.

[0446] In a further embodiment, the peptide is capable of forming a hydrogel by selfassembly in an aqueous medium, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I), wherein

[0447] GAR-P04562WO16 Application (final) docx X1, X2, A4, A5, and A6have the meanings as defined herein, and wherein the aqueous medium has an ionic strength between 0.0001 M and 1.5 M, preferably between 0.001 M and 0.5 M, more preferably 0.005 M and 0.3 M.

[0448] In another embodiment, the peptide is capable of forming a hydrogel by selfassembly under physiological conditions, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I), and wherein X1, X2, A4, A5, and A6have the meanings as defined herein.

[0449] The term “physiological conditions” as used herein refers to conditions that approximate the ionic strength, pH, and temperature of physiological environments, typically including: an aqueous medium having a pH between 6.8 and 7.6, preferably about 7.4; a temperature of about 37 °C; and the presence of physiological ionic strength, such as in phosphate-buffered saline (PBS) or similar buffers containing approximately 0.1-0.2 M NaCI.

[0450] Under such conditions, the inventive peptides are capable of self-assembling into three-dimensional networks that result in the formation of macroscopic hydrogels. In particular embodiments, hydrogel formation occurs at peptide concentrations of 8 wt% or less, preferably 6 wt% or less, more preferably 5 wt% or less, even more preferably 4 wt% or less, more preferably 3 wt % or less, preferably 2 wt % or less, preferably 1 wt % or less, demonstrating the high efficiency of network formation under mild, physiologically relevant conditions.

[0451] A further aspect of the present invention is directed to a hydrogel composition comprising an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by self-assembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous dispersion phase.

[0452] In a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide as disclosed herein, wherein the hydrogel is formed by non-covalent interactions and most probably by self-assembly of said peptide in said aqueous dispersion phase, and wherein the peptide is present in said hydrogel at a level of from about 0.01 % by weight to about 20%, preferably from about 0.01 % by weight to about 10% by weight, based upon the total weight of the hydrogel.

[0453] GAR-P04562WO16 Application (final) docx In a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising preferably a physiologically acceptable aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by selfassembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions, probably by self-assembly of said peptide in said aqueous dispersion phase.

[0454] In a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by self-assembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous dispersion phase, wherein the aqueous dispersion medium comprises one or more salts selected from (NH4)2SO4, Na2SO4, NaCI, KCI, CH3COONH4, NH3C(CH2OH)3CI, KH2PO4, and Na2HPO4.

[0455] The following buffers are preferred: acetate buffer, ammonium buffer (NH31 NH4+), Tris-HCI buffer, NH2C(CH2OH)3 / NH3+C(CH2OH)3buffer, TAE buffer, phosphate buffer, and phosphate buffered saline.

[0456] In a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by self-assembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous dispersion phase, wherein the composition has a pH value between 4.0 and 9.0, preferably between 4.5 and 8.5, more preferably between 4.8 and 8.0, still more preferably between 5.0 and 7.5.

[0457] In a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by self-assembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous dispersion phase, wherein the hydrogel has a pH value between 4.0 and 8.5, preferably between 4.5 and 8.0.

[0458] In a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by self-assembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous

[0459] GAR-P04562WO16 Application (final) docx dispersion phase, and wherein the composition has an ionic strength between 0.0001 M and 1.5 M, preferably between 0.001 M and 0.5 M, more preferably 0.005 M and 0.3 M. The inventive self-assembling covers a broad range of storage moduli from 10 Pa to 100,000 Pa. Thus, in a preferred embodiment, the hydrogel composition comprises an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide capable of forming a hydrogel by self-assembly as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous dispersion phase, and wherein the composition has a storage modulus in the range of about 10 Pa to about 100,000 Pa.

[0460] Description of the invention Definitions

[0461] Throughout this specification amino acid residues will be denoted by the three-letter abbreviation or single-letter code as follows:

[0462] GAR-P04562WO16 Application (final) docx The term “neutral amino acid”, as used herein, refers to any proteinogenic and non- proteinogenic amino acid having an aliphatic or cyclic side chain or no side chain, including but not limiting to glycine (Gly, G), alanine (Ala, A), proline (Pro, P), leucine (Leu, L), valine (Vai, V), isoleucine (lie, I), and methionine (Met, M).

[0463] The term “small neutral amino acid”, as used herein, refers to any proteinogenic and non-proteinogenic neutral amino acid having a volume of less then 120 A3, including but not limiting to glycine (Gly, G), alanine (Ala, A), and proline (Pro, P).

[0464] The term “large neutral amino acid”, as used herein, refers to any proteinogenic and non-proteinogenic neutral amino acid having a volume of more then 120 A3(van der Waals volume A3; 1 A = 100 pm = 0.1 nm = 10’10m), including but not limiting to leucine (Leu, L), valine (Vai, V), isoleucine (lie, I), and methionine (Met, M).

[0465] The term “neutral hydrophilic amino acid”, as used herein, refers to any proteinogenic and non-proteinogenic hydrophilic amino acid having a protic functional group, but lacking an acidic or basic group, including but not limiting to serine (Ser, S), threonine (Thr, T), and cysteine (Cys, C).

[0466] The term “aromatic amino acid”, as used herein, refers to any proteinogenic and non-proteinogenic amino acid having an aromatic group, including but not limiting to phenylalanine (Phe, F), tryptophane (Trp, W), and tyrosine (Tyr, Y).

[0467] The term “amino acid amide”, as used herein, refers to any proteinogenic and non- proteinogenic hydrophilic amino acid having an amide functional group in the side chain, including but not limiting to asparagine (Asn, N), and glutamine (Gin, Q).

[0468] The term “acidic amino acid” refers to any proteinogenic and non-proteinogenic amino acid having an acidic (carboxy) group in the side chain, including but not limiting to aspartic acid (Asp, D), and glutamic acid (Glu, E).

[0469] The term “basic amino acid”, as used herein, refers to any proteinogenic and non- proteinogenic amino acid having a basic (amino) group in the side chain, including but not limiting to lysine (Lys, K), arginine (Arg, R), and histidine(His, H).

[0470] Surprisingly it was found that a peptide capable of forming a hydrogel by selfassembly consisting of 6 to 12 amino acids having the following amino acid sequence of general formula (I):

[0471] GAR-P04562WO16 Application (final) docx X1-A4-A5-A6-X2(I) wherein

[0472] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0473] C-A1-A2-A3-; wherein C represents the amino acid cysteine;

[0474] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0475] -A7-A8-A9-A10-A11;

[0476] A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;

[0477] A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;

[0478] A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;

[0479] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0480] A7and A8represent independently of each other a neutral amino acid;

[0481] A9represents a basic amino acid, or an amino acid amide;

[0482] A10represents a basic amino acid, or an aromatic amino acid;

[0483] A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide, solves the objective of the present invention in an optimal way.

[0484] The peptides capable of forming a hydrogel by self-assembly according to the present invention consist of 6 to 12 amino acids. For example, excluded from the scope of the present application are peptides of the general formulae H-A4-A5-A6- H, H-A3-A4-A5-A6-H, H-A4-A5-A6-A7-H, H-A2-A3-A4-A5-A6-H, H-A4-A5-A6- A7-A8-H and H-A3-A4-A5-A6-A7-H.

[0485] Moreover, formulated differently, the peptides according to the present invention consist of 6 to 12 amino acids. In some preferred embodiments, the self-assembling peptides according to the present invention consist of 7 to 12 amino acids, more preferably 8 to 12 amino acids, more preferably 9 to 12 amino acids, even more preferably 10 or 12 amino acids. In particular preferred embodiments, the selfassembling peptides according to the present invention consist of 12 amino acids. In some preferred embodiments, the self-assembling peptides according to the present invention consist of 6 to 11 amino acids, more preferably 7 to 11 amino acids, more preferably 8 to 11 amino acids, more preferably 9 to 11 amino acids, even more preferably 10 or 11 amino acids. In particular preferred embodiments, the selfassembling peptides according to the present invention consist of 11 amino acids. Furthermore, in some embodiments, wherein the self-assembling peptides according

[0486] GAR-P04562WO16 Application (final) docx to the present invention consist of 9 - 12 amino acids, it is also preferred that A3represents a basic amino acid, or an amino acid amide, wherein the amide is in the side chain.

[0487] Preferred are peptides capable of forming a hydrogel by self-assembly consisting of 6 to 12 amino acids having the amino acid sequence of general formula (I), wherein A1represents an amino acid selected from G and A;

[0488] A2represents an amino acid selected from Y, F, and W;

[0489] A3represents an amino acid selected from R, K and L;

[0490] A4represents an amino acid selected from G, and A;

[0491] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0492] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0493] A7represents an amino acid selected from L, I, and V;

[0494] A8represents an amino acid selected from A, G, and V;

[0495] A9represents an amino acid selected from K, N, and Q;

[0496] A10represents an amino acid selected from W, and F;

[0497] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G; and more preferably

[0498] A1represents an amino acid selected from G and A;

[0499] A2represents an amino acid selected from Y, and F;

[0500] A3represents an amino acid selected from R, K and L;

[0501] A4represents an amino acid selected from G, and A;

[0502] A5represents an amino acid selected from I, and Y;

[0503] A6represents an amino acid selected from S, T, C, N, and Y;

[0504] A7represents an amino acid selected from L, and I;

[0505] A8represents an amino acid selected from A, and G;

[0506] A9represents an amino acid selected from K and N;

[0507] A10represents an amino acid selected from W, and F;

[0508] A11represents an amino acid selected from M, M-NH2, L, I, and V; and still more preferably

[0509] A1represents G;

[0510] A2represents an amino acid selected from Y, and F;

[0511] A3represents an amino acid selected from R, K and L;

[0512] A4represents G;

[0513] A5represents an amino acid selected from I, and Y;

[0514] A6represents an amino acid selected from S and T;

[0515] A7represents L;

[0516] A8represents A;

[0517] GAR-P04562WO16 Application (final) docx A9represents an amino acid selected from K and N;

[0518] A10represents W;

[0519] A11represents an amino acid selected from M, M-NH2, and V.

[0520] Preferred are peptides capable of forming a hydrogel by self-assembly consisting of 6 to 12 amino acids having the amino acid sequence of general formula (I), wherein A1represents an amino acid selected from G and A;

[0521] A2represents an amino acid selected from Y, F, and W;

[0522] A3represents an amino acid selected from R, K and L;

[0523] A4represents an amino acid selected from G, and A;

[0524] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0525] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0526] A7represents an amino acid selected from L, I, and V;

[0527] A8represents an amino acid selected from A, G, and V;

[0528] A9represents an amino acid selected from K, N, and Q;

[0529] A10represents an amino acid selected from W, and F;

[0530] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G; and more preferably

[0531] A1represents an amino acid selected from G and A;

[0532] A2represents an amino acid selected from Y, and F;

[0533] A3represents an amino acid selected from R, K and L;

[0534] A4represents an amino acid selected from G, and A;

[0535] A5represents an amino acid selected from I, and Y;

[0536] A6represents an amino acid selected from S, T, C, N, and Y;

[0537] A7represents an amino acid selected from L, and I;

[0538] A8represents an amino acid selected from A, and G;

[0539] A9represents an amino acid selected from K and N;

[0540] A10represents an amino acid selected from W, and F;

[0541] A11represents an amino acid selected from M, M-NH2, L, I, and V; and still more preferably

[0542] A1represents G;

[0543] A2represents an amino acid selected from Y, and F;

[0544] A3represents an amino acid selected from R, K and L;

[0545] A4represents G;

[0546] A5represents an amino acid selected from I, and Y;

[0547] A6represents an amino acid selected from S and T;

[0548] A7represents L;

[0549] A8represents A;

[0550] GAR-P04562WO16 Application (final) docx A9represents an amino acid selected from K and N;

[0551] A10represents W;

[0552] A11represents an amino acid selected from M, M-NH2, and V; with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0553] Preferred are peptides capable of forming a hydrogel by self-assembly consisting of

[0554] 6 to 11 amino acids having the general formula (I) X1-A4-A5-A6-X2, wherein X1represents -H and X2represents -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11; or wherein

[0555] X2represents -H and X1represents A1-A2-A3-; and the residues A1- A11have the meanings as disclosed herein.

[0556] Preferred are peptides capable of forming a hydrogel by self-assembly consisting of

[0557] 7 to 12 amino acids having the general formula (I) X1-A4-A5-A6-X2, wherein X1represents C and X2represents -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11; or wherein

[0558] X2represents -H and X1represents C-A1-A2-A3-; and the residues A1- A11have the meanings as disclosed herein.

[0559] Preferred are peptides capable of forming a hydrogel by self-assembly consisting of

[0560] 6 to 11 amino acids having the general formula (I) X1-A4-A5-A6-X2, wherein X1represents A3- and X2represents -A7-A8, -A7-A8-A9,

[0561] -A7-A8-A9-A10, or -A7-A8-A9-A10-A11; or wherein

[0562] X2represents -A7, and X1represents A1-A2-A3-, or A2-A3-; and the residues A1- A11have the meanings as disclosed herein.

[0563] Preferred are peptides capable of forming a hydrogel by self-assembly consisting of

[0564] 6 to 12 amino acids having the general formula (I) X1-A4-A5-A6-X2, wherein X1represents A2-A3- and X2represents -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11; or wherein

[0565] X2represents -A7-A8and X1represents A1-A2-A3-, A2-A3- or A3-; and the residues A1- A11have the meanings as disclosed herein.

[0566] GAR-P04562WO16 Application (final) docx In some embodiments, the present invention relates to a self-assembling peptide consisting of 6 to 12 amino acids having the following amino acid sequence (SEQ ID NO: 1 ):

[0567] X1’-G-A5-S-L-A-N-X7’ wherein

[0568] X1’ represents -H, C, or G-

[0569] A5represents the amino acid

[0570] X7’ represents a -H or -W-X

[0571] A3represents the amino acid

[0572] X7” represents -H or -A11; a

[0573] A11represents the amino acid M, M-NH2, or V.

[0574] In some embodiments, the present invention relates to a self-assembling peptide consisting of 6 to 12 amino acids having the following amino acid sequence (SEQ ID NO: 1 ):

[0575] X1’-G-A5-S-L-A-N-X7’ wherein

[0576] X1’ represents -H, C or G-

[0577] A5represents the amino acid

[0578] X7’ represents a -H or -W-

[0579] A3represents the amino acid

[0580] X7” represents -H or -A11;

[0581] A11represents the amino acid M, M-NH2, or V, with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0582] In some embodiments, the present invention relates to a self-assembling peptide consisting of 6 to 11 amino acids having the following amino acid sequence (SEQ ID NO: 1 ):

[0583] X1’-G-A5-S-L-A-N-X7’ wherein

[0584] X1’ represents -H, or G-Y-

[0585] A5represents the amino acid

[0586] X7’ represents a -H or -W-X

[0587] A3represents the amino acid

[0588] X7” represents -H or -A11; a

[0589] A11represents the amino acid M, M-NH2, or V.

[0590] GAR-P04562WO16 Application (final) docx In some embodiments, the present invention relates to a self-assembling peptide consisting of 6 to 11 amino acids having the following amino acid sequence (SEQ ID NO: 1 ):

[0591] X1’-G-A5-S-L-A-N-X7’ wherein

[0592] X1’ represents -H, or G-Y-

[0593] A5represents the amino acid

[0594] X7’ represents a -H or -W-X

[0595] A3represents the amino acid

[0596] X7” represents -H or -A11; a

[0597] A11represents the amino acid M, M-NH2, or V, with the proviso that the self-assembling peptide does not consist of the amino acid sequence GISLAN (SEQ ID NO: 3).

[0598] Furthermore, peptides capable of forming a hydrogel by self-assembly consisting of 6 to 12 amino acids having the following general formulae are preferred:

[0599] X1-A4-A5-A6-A7-X3, X1-A4-A5-A6-A7-A8-X5, X1-A4-A5-A6-A7-A8-A9-X7, X1-A4-A5-A6-A7-A8-A9-A10-X8, X1-A4-A5-A6-A7-A8-A9-A10-A11,

[0600] X4-A3-A4-A5-A6-X2, X6-A2-A3-A4-A5-A6-X2, A1-A2-A3-A4-A5-A6-X2,

[0601] X4-A3-A4-A5-A6-A7-X3, X6-A2-A3-A4-A5-A6-A7-X3, X4-A3-A4-A5-A6-A7-A8-X5, wherein

[0602] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0603] C-A1-A2-A3-; wherein C represents the amino acid cysteine; preferably X1represents -H, A1-A2-A3-, A2-A3-, or A3-;

[0604] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0605] -A7-A8-A9-A10-A11;

[0606] X3represents -H, -A8, -A8-A9, -A8-A9-A10, or -A8-A9-A10-A11;

[0607] GAR-P04562WO16 Application (final) docx X4represents -H, A1-A2-, or A2-;

[0608] X5represents -H, -A9, -A9-A10, or -A9-A10-A11;

[0609] X6represents -H, or A1-;

[0610] X7represents -H, -A10, or -A10-A11;

[0611] X8represents -H, or -A11; wherein

[0612] A1represents an amino acid selected from G and A;

[0613] A2represents an amino acid selected from Y, F, and W;

[0614] A3represents an amino acid selected from R, K and L;

[0615] A4represents an amino acid selected from G, and A;

[0616] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0617] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0618] A7represents an amino acid selected from L, I, and V;

[0619] A8represents an amino acid selected from A, G, and V;

[0620] A9represents an amino acid selected from K, N, and Q;

[0621] A10represents an amino acid selected from W, and F;

[0622] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G; and more preferably wherein

[0623] A1represents an amino acid selected from G and A;

[0624] A2represents an amino acid selected from Y, and F;

[0625] A3represents an amino acid selected from R, K and L;

[0626] A4represents an amino acid selected from G, and A;

[0627] A5represents an amino acid selected from I, and Y;

[0628] A6represents an amino acid selected from S, T, C, N, and Y;

[0629] A7represents an amino acid selected from L, and I;

[0630] A8represents an amino acid selected from A, and G;

[0631] A9represents an amino acid selected from K and N;

[0632] A10represents an amino acid selected from W, and F;

[0633] A11represents an amino acid selected from M, M-NH2, L, I, and V; and still more preferably wherein

[0634] A1represents G;

[0635] A2represents an amino acid selected from Y, and F;

[0636] A3represents an amino acid selected from R, K and L;

[0637] A4represents G;

[0638] A5represents an amino acid selected from I, and Y;

[0639] A6represents an amino acid selected from S and T;

[0640] A7represents L;

[0641] A8represents A;

[0642] GAR-P04562WO16 Application (final) docx A9represents an amino acid selected from K and N;

[0643] A10represents W;

[0644] A11represents an amino acid selected from M, M-NH2, and V.

[0645] Moreover, in preferred peptides capable of forming a hydrogel by self-assembly the residue

[0646] A1represents G, while the residues A2- A11have the meanings as disclosed herein, or

[0647] A2represents Y or F and most preferably Y, while the residues A1, A3- A11have the meanings as disclosed herein, or

[0648] A3represents R or L and most preferably R, while the residues A1, A2, A4- A11have the meanings as disclosed herein, or

[0649] A4represents G, while the residues A1- A3and A5- A11have the meanings as disclosed herein, or

[0650] A5represents I or Y and most preferably I, while the residues A1- A4and A6- A11have the meanings as disclosed herein, or

[0651] A6represents S, T, C, N, Q, Y, A, G, and V, more preferably S, T, C, N, Q, and Y, even more preferably S, T, C, N, and Y, even more preferably, S, T, C, and N, even more preferably, S, T, and C, even more preferably S, and T, and most preferably S, while the residues A1- A5and A7- A11have the meanings as disclosed herein, or

[0652] A7represents L, while the residues A1- A6and A8- A11have the meanings as disclosed herein, or

[0653] A8represents A, while the residues A1- A7and A9- A11have the meanings as disclosed herein, or

[0654] A9represents N or K and most preferably N, while the residues A1- A8, A10and A11have the meanings as disclosed herein, or

[0655] A10represents W, while the residues A1- A9and A11have the meanings as disclosed herein, or

[0656] GAR-P04562WO16 Application (final) docx A11represents M, M-NH2, or V, more preferably M or V, still more preferably M or M-NH2, and most preferably M, while the residues A1- A10have the meanings as disclosed herein.

[0657] Furthermore, the following peptides capable of forming a hydrogel by self-assembly consisting of 6 to 12 amino acids having the general formula (I) are preferred

[0658] X1-G-|-A6-X2X1-A4-l-Q-X2X1-G-Y-A6-X2X1-A4-l-Y-X2X1-G-A5-S-X2X1-A4-l-A-X2X1-G-A5-T-X2X1-A4-l-G-X2X1-G-A5-C-X2X1-A4-l-V-X2X1-G-A5-N-X2X1-A4-Y-S-X2X1-G-A5-Q-X2X1-A4-Y-T-X2X1-G-A5-Y-X2X1-A4-Y-C-X2X1-G-A5-A-X2X1-A4-Y-N-X2X1-G-A5-G-X2X1-A4-Y-Q-X2X1-G-A5-V-X2X1-A4-Y-Y-X2X1-A4-l-S-X2X1-A4-Y-A-X2X1-A4-l-T-X2X1-A4-Y-G-X2X1-A4-l-C-X2X1-A4-Y-V-X2

[0659] X1-A4-l-N-X2wherein

[0660] X1, X2, A4, A5, and A6have the meanings as disclosed herein and preferably

[0661] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0662] C-A1-A2-A3-; wherein C represents the amino acid cysteine; preferably X1represents -H, A1-A2-A3-, A2-A3- or A3-;

[0663] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0664] -A7-A8-A9-A10-A11; wherein

[0665] A1represents an amino acid selected from G and A;

[0666] A2represents an amino acid selected from Y, F, and W;

[0667] A3represents an amino acid selected from R, K and L;

[0668] A4represents an amino acid selected from G, and A;

[0669] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0670] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0671] A7represents an amino acid selected from L, I, and V;

[0672] A8represents an amino acid selected from A, G, and V;

[0673] GAR-P04562WO16 Application (final) docx A9represents an amino acid selected from K, N, and Q;

[0674] A10represents an amino acid selected from W, and F;

[0675] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G; and more preferably wherein

[0676] A1represents an amino acid selected from G and A;

[0677] A2represents an amino acid selected from Y, and F;

[0678] A3represents an amino acid selected from R, K and L;

[0679] A4represents an amino acid selected from G, and A;

[0680] A5represents an amino acid selected from I, and Y;

[0681] A6represents an amino acid selected from S, T, C, N, and Y;

[0682] A7represents an amino acid selected from L, and I;

[0683] A8represents an amino acid selected from A, and G;

[0684] A9represents an amino acid selected from K and N;

[0685] A10represents an amino acid selected from W, and F;

[0686] A11represents an amino acid selected from M, M-NH2, L, I, and V; and still more preferably wherein

[0687] A1represents G;

[0688] A2represents an amino acid selected from Y, and F;

[0689] A3represents an amino acid selected from R, K and L;

[0690] A4represents G;

[0691] A5represents an amino acid selected from I, and Y;

[0692] A6represents an amino acid selected from S and T;

[0693] A7represents L;

[0694] A8represents A;

[0695] A9represents an amino acid selected from K and N;

[0696] A10represents W;

[0697] A11represents an amino acid selected from M, M-NH2, and V.

[0698] Furthermore, the following peptides capable of forming a hydrogel by self-assembly consisting of 6 to 12 amino acids having of general formula (I) are even more preferred

[0699] X1-G-Y-S-X2X1-G-l-Q-X2X1-G-l-S-X2X1-G-Y-Y-X2X1-G-Y-T-X2X1-G-l-Y-X2X1-G-|-T-X2X1-G-Y-A-X2X1-G-Y-C-X2X1-G-l-A-X2X1-G-l-C-X2X1-G-Y-G-X2X1-G-Y-N-X2X1-G-|-G-X2

[0700] GAR-P04562WO16 Application (final) docx X1-G-l-N-X2X1-G-Y-V-X2

[0701] X1-G-Y-Q-X2X1-G-l-V-X2wherein

[0702] X1, X2have the meanings as disclosed herein and preferably

[0703] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or

[0704] C-A1-A2-A3-; wherein C represents the amino acid cysteine; preferably X1represents -H, A1-A2-A3-, A2-A3- or A3-;

[0705] X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or

[0706] -A7-A8-A9-A10-A11; wherein

[0707] A1represents an amino acid selected from G and A;

[0708] A2represents an amino acid selected from Y, F, and W;

[0709] A3represents an amino acid selected from R, K and L;

[0710] A7represents an amino acid selected from L, I, and V;

[0711] A8represents an amino acid selected from A, G, and V;

[0712] A9represents an amino acid selected from K, N, and Q;

[0713] A10represents an amino acid selected from W, and F;

[0714] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G; and more preferably wherein

[0715] A1represents an amino acid selected from G and A;

[0716] A2represents an amino acid selected from Y, and F;

[0717] A3represents an amino acid selected from R, K and L;

[0718] A7represents an amino acid selected from L, and I;

[0719] A8represents an amino acid selected from A, and G;

[0720] A9represents an amino acid selected from K and N;

[0721] A10represents an amino acid selected from W, and F;

[0722] A11represents an amino acid selected from M, M-NH2, L, I, and V; and still more preferably wherein

[0723] A1represents G;

[0724] A2represents an amino acid selected from Y, and F;

[0725] A3represents an amino acid selected from R, K and L;

[0726] A7represents L;

[0727] A8represents A;

[0728] A9represents an amino acid selected from K and N;

[0729] A10represents W;

[0730] A11represents an amino acid selected from M, M-NH2, and V.

[0731] GAR-P04562WO16 Application (final) docx ABK "

[0732] 40

[0733] Furthermore, peptides capable of forming a hydrogel by self-assembly consisting of 6 to 12 amino acids having the following general formulae are preferred:

[0734] X1-G-l-A6-L-X3, X1-G-Y-A6-L-X3, X1-G-A5-S-L-X3, X1-G-A5-T-L-X3, X1-G-A5-C-L-X3, X1-G-A5-N-L-X3, X1-G-A5-Q-L-X3, X1-G-A5-Y-L-X3, X1-G-A5-A-L-X3, X1-G-A5-G-L-X3, X1-G-A5-V-L-X3, X1-A4-l-S-L-X3X1-A4-l-T-L-X3X1-A4-l-C-L-X3X1-A4-l-N-L-X3X1-A4-l-Q-L-X3X1-A4-l-Y-L-X3X1-A4-l-A-L-X3X1-A4-l-G-L-X3, X1-A4-l-V-L-X3, X1-A4-Y-S-L-X3, X1-A4-Y-T-L-X3X1-A4-Y-C-L-X3, X1-A4-Y-N-L-X3X1-A4-Y-Q-L-X3, X1-A4-Y-Y-L-X3X1-A4-Y-A-L-X3, X1-A4-Y-G-L-X3X1-A4-Y-V-L-X3,

[0735] X1-G-Y-S-L-X3(SEQ ID NO: 31 ), X1-G-l-S-L-X3(SEQ ID NO: 32), X1-G-Y-T-L-X3(SEQ ID NO: 33), X1-G-l-T-L-X3(SEQ ID NO: 34), X1-G-Y-C-L-X3(SEQ ID NO: 322), X1-G-l-C-L-X3(SEQ ID NO: 329),

[0736] GAR-P04562WO16 Application (final) docx -ABK

[0737] 41

[0738] X1-G-Y-N-L-X3(SEQ ID NO: 323), X1-G-l-N-L-X3(SEQ ID NO: 330), X1-G-Y-Q-L-X3(SEQ ID NO: 324), X1-G-l-Q-L-X3(SEQ ID NO: 331 ), X1-G-Y-Y-L-X3(SEQ ID NO: 325), X1-G-Y-Y-L-X3(SEQ ID NO: 332), X1-G-l-A-L-X3(SEQ ID NO: 326), X1-G-Y-A-L-X3(SEQ ID NO: 333), X1-G-l-G-L-X3(SEQ ID NO: 327), X1-G-Y-G-L-X3(SEQ ID NO: 334), X1-G-l-V-L-X3(SEQ ID NO: 328), X1-G-Y-V-L-X3(SEQ ID NO: 335),

[0739] X1-G-|-A6-L-A-X5(SEQ ID NO: 35), X1-G-Y-A6-L-A-X5(SEQ ID NO: 36), X1-G-A5-S-L-A-X5(SEQ ID NO: 37), X1-G-A5-T-L-A-X5(SEQ ID NO: 38), X1-A4-|-C-L-A-X5(SEQ ID NO: 336), X1-A4-|-N-L-A-X5(SEQ ID NO: 337), X1-A4-Y-Q-L-A-X5(SEQ ID NO: 338), X1-A4-Y-Y-L-A-X5(SEQ ID NO: 339), X1-A4-Y-A-L-A-X5(SEQ ID NO: 340), X1-A4-Y-G-L-A-X5(SEQ ID NO: 341 ), X1-A4-Y-V-L-A-X5(SEQ ID NO: 342),

[0740] X1-G-Y-S-L-A-X5(SEQ ID NO: 43), X1-G-l-S-L-A-X5(SEQ ID NO: 44), X1-G-Y-T-L-A-X5(SEQ ID NO: 45), X1-G-l-T-L-A-X5(SEQ ID NO: 46), X1-G-Y-C-L-A-X5(SEQ ID NO: 343), X1-G-l-C-L-A-X5(SEQ ID NO: 350), X1-G-Y-N-L-A-X5(SEQ ID NO: 344), X1-G-l-N-L-A-X5(SEQ ID NO: 351 ), X1-G-Y-Q-L-A-X5(SEQ ID NO: 345), X1-G-l-Q-L-A-X5(SEQ ID NO: 352), X1-G-Y-Y-L-A-X5(SEQ ID NO: 346), X1-G-l-Y-L-A-X5(SEQ ID NO: 353), X1-G-Y-A-L-A-X5(SEQ ID NO: 347),

[0741] GAR-P04562WO16 Application (final) docx X1-G-|-A-L-A-X5(SEQ ID NO: 354), X1-G-Y-G-L-A-X5(SEQ ID NO: 348), X1-G-l-G-L-A-X5(SEQ ID NO: 355), X1-G-Y-V-L-A-X5(SEQ ID NO: 349), X1-G-|-V-L-A-X5(SEQ ID NO: 356),

[0742] X1-G-|-A6-L-A-K-X7(SEQ ID NO: 47), X1-G-Y-A6-L-A-K-X7(SEQ ID NO: 48), X1-G-A5-S-L-A-K-X7(SEQ ID NO: 49), X1-G-A5-T-L-A-K-X7(SEQ ID NO: 50), X1-G-A5-C-L-A-K-X7(SEQ ID NO: 357), X1-G-A5-N-L-A-K-X7(SEQ ID NO: 358), X1-G-A5-Q-L-A-K-X7(SEQ ID NO: 359), X1-G-A5-Y-L-A-K-X7(SEQ ID NO: 360), X1-G-A5-A-L-A-K-X7(SEQ ID NO: 361), X1-G-A5-G-L-A-K-X7(SEQ ID NO: 362), X1-G-A5-V-L-A-K-X7(SEQ ID NO: 363),

[0743] X1-A4-|-S-L-A-K-X7(SEQ ID NO: 51 ), X1-A4-|-T-L-A-K-X7(SEQ ID NO: 52), X1-A4-|-C-L-A-K-X7(SEQ ID NO: 364), X1-A4-|-N-L-A-K-X7(SEQ ID NO: 365), X1-A4-|-Q-L-A-K-X7(SEQ ID NO: 366), X1-A4-|-Y-L-A-K-X7(SEQ ID NO: 367), X1-A4-|-A-L-A-K-X7(SEQ ID NO: 368), X1-A4-|-G-L-A-K-X7(SEQ ID NO: 369), X1-A4-|-V-L-A-K-X7(SEQ ID NO: 370),

[0744] X1-A4-Y-S-L-A-K-X7(SEQ ID NO: 53), X1-A4-Y-T-L-A-K-X7(SEQ ID NO: 54), X1-A4-Y-C-L-A-K-X7(SEQ ID NO: 371 ), X1-A4-Y-N-L-A-K-X7(SEQ ID NO: 372), X1-A4-Y-Q-L-A-K-X7(SEQ ID NO: 373), X1-A4-Y-Y-L-A-K-X7(SEQ ID NO: 374), X1-A4-Y-A-L-A-K-X7(SEQ ID NO: 375), X1-A4-Y-G-L-A-K-X7(SEQ ID NO: 376), X1-A4-Y-V-L-A-K-X7(SEQ ID NO: 377),

[0745] GAR-P04562WO16 Application (final) docx X1-G-Y-S-L-A-K-X7(SEQ ID NO: 55), X1-G-l-S-L-A-K-X7(SEQ ID NO: 56), X1-G-Y-T-L-A-K-X7(SEQ ID NO: 57), X1-G-l-T-L-A-K-X7(SEQ ID NO: 58), X1-G-Y-C-L-A-K-X7(SEQ ID NO: 378), X1-G-l-C-L-A-K-X7(SEQ ID NO: 385), X1-G-Y-N-L-A-K-X7(SEQ ID NO: 379), X1-G-l-N-L-A-K-X7(SEQ ID NO: 386), X1-G-Y-Q-L-A-K-X7(SEQ ID NO: 380), X1-G-l-Q-L-A-K-X7(SEQ ID NO: 387), X1-G-Y-Y-L-A-K-X7(SEQ ID NO: 381 ), X1-G-l-Y-L-A-K-X7(SEQ ID NO: 388), X1-G-Y-A-L-A-K-X7(SEQ ID NO: 382), X1-G-l-A-L-A-K-X7(SEQ ID NO: 389), X1-G-Y-G-L-A-K-X7(SEQ ID NO: 383), X1-G-l-G-L-A-K-X7(SEQ ID NO: 390), X1-G-Y-V-L-A-K-X7(SEQ ID NO: 384), X1-G-l-V-L-A-K-X7(SEQ ID NO: 391 ),

[0746] X1-G-l-A6-L-A-N-X7(SEQ ID NO: 59), X1-G-Y-A6-L-A-N-X7(SEQ ID NO: 60), X1-G-A5-S-L-A-N-X7(SEQ ID NO: 61 ), X1-G-A5-T-L-A-N-X7(SEQ ID NO: 62), X1-G-A5-C-L-A-N-X7(SEQ ID NO: 392), X1-G-A5-N-L-A-N-X7(SEQ ID NO: 393), X1-G-A5-Q-L-A-N-X7(SEQ ID NO: 394), X1-G-A5-Y-L-A-N-X7(SEQ ID NO: 395), X1-G-A5-A-L-A-N-X7(SEQ ID NO: 396), X1-G-A5-G-L-A-N-X7(SEQ ID NO: 397), X1-G-A5-V-L-A-N-X7(SEQ ID NO: 398),

[0747] X1-A4-l-S-L-A-N-X7(SEQ ID NO: 63), X1-A4-l-T-L-A-N-X7(SEQ ID NO: 64), X1-A4-l-C-L-A-N-X7(SEQ ID NO: 399), X1-A4-l-N-L-A-N-X7(SEQ ID NO: 400), X1-A4-l-Q-L-A-N-X7(SEQ ID NO: 401 ), X1-A4-l-Y-L-A-N-X7(SEQ ID NO: 402), X1-A4-l-A-L-A-N-X7(SEQ ID NO: 403),

[0748] GAR-P04562WO16 Application (final) docx X1-A4-l-G-L-A-N-X7(SEQ ID NO: 404), X1-A4-l-V-L-A-N-X7(SEQ ID NO: 405),

[0749] X1-A4-Y-S-L-A-N-X7(SEQ ID NO: 65), X1-A4-Y-T-L-A-N-X7(SEQ ID NO: 66), X1-A4-Y-C-L-A-N-X7(SEQ ID NO: 406), X1-A4-Y-N-L-A-N-X7(SEQ ID NO: 407), X1-A4-Y-Q-L-A-N-X7(SEQ ID NO: 408), X1-A4-Y-Y-L-A-N-X7(SEQ ID NO: 409), X1-A4-Y-A-L-A-N-X7(SEQ ID NO: 410), X1-A4-Y-G-L-A-N-X7(SEQ ID NO: 411 ), X1-A4-Y-V-L-A-N-X7(SEQ ID NO: 412),

[0750] X1-G-Y-S-L-A-N-X7(SEQ ID NO: 67), X1-G-l-S-L-A-N-X7(SEQ ID NO: 68), X1-G-Y-T-L-A-N-X7(SEQ ID NO: 69), X1-G-l-T-L-A-N-X7(SEQ ID NO: 70), X1-G-Y-C-L-A-N-X7(SEQ ID NO: 413), X1-G-l-C-L-A-N-X7(SEQ ID NO: 420), X1-G-Y-N-L-A-N-X7(SEQ ID NO: 414), X1-G-l-N-L-A-N-X7(SEQ ID NO: 421 ), X1-G-Y-Q-L-A-N-X7(SEQ ID NO: 415), X1-G-l-Q-L-A-N-X7(SEQ ID NO: 422), X1-G-Y-Y-L-A-N-X7(SEQ ID NO: 416), X1-G-l-Y-L-A-N-X7(SEQ ID NO: 423), X1-G-Y-A-L-A-N-X7(SEQ ID NO: 417), X1-G-l-A-L-A-N-X7(SEQ ID NO: 424), X1-G-Y-G-L-A-N-X7(SEQ ID NO: 418), X1-G-l-G-L-A-N-X7(SEQ ID NO: 425), X1-G-Y-V-L-A-N-X7(SEQ ID NO: 419), X1-G-l-V-L-A-N-X7(SEQ ID NO: 426),

[0751] X1-G-l-A6-L-A-N-W-X8(SEQ ID NO: 71 ), X1-G-Y-A6-L-A-N-W-X8(SEQ ID NO: 72), X1-G-A5-S-L-A-N-W-X8(SEQ ID NO: 73), X1-G-A5-T-L-A-N-W-X8(SEQ ID NO: 74), X1-G-A5-C-L-A-N-W-X8(SEQ ID NO: 427), X1-G-A5-N-L-A-N-W-X8(SEQ ID NO: 428),

[0752] GAR-P04562WO16 Application (final) docx X1-G-A5-Q-L-A-N-W-X8(SEQ ID NO: 429), X1-G-A5-Y-L-A-N-W-X8(SEQ ID NO: 430), X1-G-A5-A-L-A-N-W-X8(SEQ ID NO: 431 ), X1-G-A5-G-L-A-N-W-X8(SEQ ID NO: 432), X1-G-A5-V-L-A-N-W-X8(SEQ ID NO: 433),

[0753] X1-A4-l-S-L-A-N-W-X8(SEQ ID NO: 75), X1-A4-l-T-L-A-N-W-X8(SEQ ID NO: 76), X1-A4-l-C-L-A-N-W-X8(SEQ ID NO: 434), X1-A4-l-N-L-A-N-W-X8(SEQ ID NO: 435), X1-A4-l-Q-L-A-N-W-X8(SEQ ID NO: 436), X1-A4-l-Y-L-A-N-W-X8(SEQ ID NO: 437), X1-A4-l-A-L-A-N-W-X8(SEQ ID NO: 438), X1-A4-l-G-L-A-N-W-X8(SEQ ID NO: 439), X1-A4-l-V-L-A-N-W-X8(SEQ ID NO: 440),

[0754] X1-A4-Y-S-L-A-N-W-X8(SEQ ID NO: 77), X1-A4-Y-T-L-A-N-W-X8(SEQ ID NO: 78), X1-A4-Y-C-L-A-N-W-X8(SEQ ID NO: 441 ), X1-A4-Y-N-L-A-N-W-X8(SEQ ID NO: 442), X1-A4-Y-Q-L-A-N-W-X8(SEQ ID NO: 443), X1-A4-Y-Y-L-A-N-W-X8(SEQ ID NO: 444), X1-A4-Y-A-L-A-N-W-X8(SEQ ID NO: 445), X1-A4-Y-G-L-A-N-W-X8(SEQ ID NO: 446), X1-A4-Y-V-L-A-N-W-X8(SEQ ID NO: 447),

[0755] X1-G-Y-S-L-A-N-W-X8(SEQ ID NO: 79), X1-G-l-S-L-A-N-W-X8(SEQ ID NO: 80), X1-G-Y-T-L-A-N-W-X8(SEQ ID NO: 81 ), X1-G-l-T-L-A-N-W-X8(SEQ ID NO: 82), X1-G-Y-C-L-A-N-W-X8(SEQ ID NO: 448), X1-G-l-C-L-A-N-W-X8(SEQ ID NO: 455), X1-G-Y-N-L-A-N-W-X8(SEQ ID NO: 449), X1-G-l-N-L-A-N-W-X8(SEQ ID NO: 456), X1-G-Y-Q-L-A-N-W-X8(SEQ ID NO: 450), X1-G-l-Q-L-A-N-W-X8(SEQ ID NO: 457), X1-G-Y-Y-L-A-N-W-X8(SEQ ID NO: 451 ), X1-G-l-Y-L-A-N-W-X8(SEQ ID NO: 458),

[0756] GAR-P04562WO16 Application (final) docx X1-G-Y-A-L-A-N-W-X8(SEQ ID NO: 452), X1-G-l-A-L-A-N-W-X8(SEQ ID NO: 459), X1-G-Y-G-L-A-N-W-X8(SEQ ID NO: 453), X1-G-l-G-L-A-N-W-X8(SEQ ID NO: 460), X1-G-Y-V-L-A-N-W-X8(SEQ ID NO: 454), X1-G-l-V-L-A-N-W-X8(SEQ ID NO: 461 ),

[0757] X1-G-l-A6-L-A-N-W-M (SEQ ID NO: 83), X1-G-Y-A6-L-A-N-W-M (SEQ ID NO: 84), X1-G-A5-S-L-A-N-W-M (SEQ ID NO: 85), X1-G-A5-T-L-A-N-W-M (SEQ ID NO: 86), X1-G-A5-C-L-A-N-W-M (SEQ ID NO: 462), X1-G-A5-N-L-A-N-W-M (SEQ ID NO: 463), X1-G-A5-Q-L-A-N-W-M (SEQ ID NO: 464), X1-G-A5-Y-L-A-N-W-M (SEQ ID NO: 465), X1-G-A5-A-L-A-N-W-M (SEQ ID NO: 466), X1-G-A5-G-L-A-N-W-M (SEQ ID NO: 467), X1-G-A5-V-L-A-N-W-M (SEQ ID NO: 468),

[0758] X1-A4-l-S-L-A-N-W-M (SEQ ID NO: 87), X1-A4-l-T-L-A-N-W-M (SEQ ID NO: 88), X1-A4-l-C-L-A-N-W-M (SEQ ID NO: 469), X1-A4-l-N-L-A-N-W-M (SEQ ID NO: 470), X1-A4-l-Q-L-A-N-W-M (SEQ ID NO: 471 ), X1-A4-l-Y-L-A-N-W-M (SEQ ID NO: 472), X1-A4-l-A-L-A-N-W-M (SEQ ID NO: 473), X1-A4-l-G-L-A-N-W-M (SEQ ID NO: 474), X1-A4-l-V-L-A-N-W-M (SEQ ID NO: 475),

[0759] X1-A4-Y-S-L-A-N-W-M (SEQ ID NO: 89), X1-A4-Y-T-L-A-N-W-M (SEQ ID NO: 90), X1-A4-Y-C-L-A-N-W-M (SEQ ID NO: 476), X1-A4-Y-N-L-A-N-W-M (SEQ ID NO: 477), X1-A4-Y-Q-L-A-N-W-M (SEQ ID NO: 478), X1-A4-Y-Y-L-A-N-W-M (SEQ ID NO: 479), X1-A4-Y-A-L-A-N-W-M (SEQ ID NO: 480), X1-A4-Y-G-L-A-N-W-M (SEQ ID NO: 481 ), X1-A4-Y-V-L-A-N-W-M (SEQ ID NO: 482),

[0760] GAR-P04562WO16 Application (final) docx ABK "

[0761] 47

[0762] X1-G-Y-S-L-A-N-W-M (SEQ ID NO: 91 ), X1-G-l-S-L-A-N-W-M (SEQ ID NO: 92), X1-G-Y-T-L-A-N-W-M (SEQ ID NO: 93), X1-G-l-T-L-A-N-W-M (SEQ ID NO: 94), X1-G-Y-C-L-A-N-W-M (SEQ ID NO: 483), X1-G-l-C-L-A-N-W-M (SEQ ID NO: 490), X1-G-Y-N-L-A-N-W-M (SEQ ID NO: 484), X1-G-l-N-L-A-N-W-M (SEQ ID NO: 491), X1-G-Y-Q-L-A-N-W-M (SEQ ID NO: 485), X1-G-l-Q-L-A-N-W-M (SEQ ID NO: 492), X1-G-Y-Y-L-A-N-W-M (SEQ ID NO: 486), X1-G-l-Y-L-A-N-W-M (SEQ ID NO: 493), X1-G-Y-A-L-A-N-W-M (SEQ ID NO: 487), X1-G-l-A-L-A-N-W-M (SEQ ID NO: 494), X1-G-Y-G-L-A-N-W-M (SEQ ID NO: 495), X1-G-l-G-L-A-N-W-M (SEQ ID NO: 488), X1-G-Y-V-L-A-N-W-M (SEQ ID NO: 496), X1-G-l-V-L-A-N-W-M (SEQ ID NO: 489),

[0763] X1-G-I-A6-L-A-N-W-M-NH2(SEQ ID NO: 95), X1-G-Y-A6-L-A-N-W-M-NH2(SEQ ID NO: 96), X1-G-A5-S-L-A-N-W-M-NH2(SEQ ID NO: 97), X1-G-A5-T-L-A-N-W-M-NH2(SEQ ID NO: 98), X1-G-A5-C-L-A-N-W-M-NH2(SEQ ID NO: 497), X1-G-A5-N-L-A-N-W-M-NH2(SEQ ID NO: 498), X1-G-A5-Q-L-A-N-W-M-NH2(SEQ ID NO: 499), X1-G-A5-Y-L-A-N-W-M-NH2(SEQ ID NO: 500), X1-G-A5-A-L-A-N-W-M-NH2(SEQ ID NO: 501 ), X1-G-A5-G-L-A-N-W-M-NH2(SEQ ID NO: 502), X1-G-A5-V-L-A-N-W-M-NH2(SEQ ID NO: 503),

[0764] X1-A4-I-S-L-A-N-W-M-NH2(SEQ ID NO: 99), X1-A4-I-T-L-A-N-W-M-NH2(SEQ ID NO: 100), X1-A4-I-C-L-A-N-W-M-NH2(SEQ ID NO: 504), X1-A4-I-N-L-A-N-W-M-NH2(SEQ ID NO: 505), X1-A4-I-Q-L-A-N-W-M-NH2(SEQ ID NO: 506), X1-A4-I-Y-L-A-N-W-M-NH2(SEQ ID NO: 507),

[0765] GAR-P04562WO16 Application (final) docx X1-A4-I-A-L-A-N-W-M-NH2(SEQ ID NO: 508), X1-A4-I-G-L-A-N-W-M-NH2(SEQ ID NO: 509), X1-A4-I-V-L-A-N-W-M-NH2(SEQ ID NO: 510),

[0766] X1-A4-Y-S-L-A-N-W-M-NH2(SEQ ID NO: 111 ), X1-A4-Y-T-L-A-N-W-M-NH2(SEQ ID NO: 112), X1-A4-Y-C-L-A-N-W-M-NH2(SEQ ID NO: 511 ), X1-A4-Y-N-L-A-N-W-M-NH2(SEQ ID NO: 512), X1-A4-Y-Q-L-A-N-W-M-NH2(SEQ ID NO: 513), X1-A4-Y-Y-L-A-N-W-M-NH2(SEQ ID NO: 514), X1-A4-Y-A-L-A-N-W-M-NH2(SEQ ID NO: 515), X1-A4-Y-G-L-A-N-W-M-NH2(SEQ ID NO: 516), X1-A4-Y-V-L-A-N-W-M-NH2(SEQ ID NO: 517),

[0767] X1-G-Y-S-L-A-N-W-M-NH2(SEQ ID NO: 113), X1-G-I-S-L-A-N-W-M-NH2(SEQ ID NO: 114), X1-G-Y-T-L-A-N-W-M-NH2(SEQ ID NO: 115), X1-G-I-T-L-A-N-W-M-NH2(SEQ ID NO: 116), X1-G-Y-C-L-A-N-W-M-NH2(SEQ ID NO: 518), X1-G-I-C-L-A-N-W-M-NH2(SEQ ID NO: 525), X1-G-Y-N-L-A-N-W-M-NH2(SEQ ID NO: 519), X1-G-I-N-L-A-N-W-M-NH2(SEQ ID NO: 526), X1-G-Y-Q-L-A-N-W-M-NH2(SEQ ID NO: 520), X1-G-I-Q-L-A-N-W-M-NH2(SEQ ID NO: 527), X1-G-Y-Y-L-A-N-W-M-NH2(SEQ ID NO: 521 ), X1-G-I-Y-L-A-N-W-M-NH2(SEQ ID NO: 528), X1-G-Y-A-L-A-N-W-M-NH2(SEQ ID NO: 522), X1-G-I-A-L-A-N-W-M-NH2(SEQ ID NO: 529), X1-G-Y-G-L-A-N-W-M-NH2(SEQ ID NO: 523), X1-G-I-G-L-A-N-W-M-NH2(SEQ ID NO: 530), X1-G-Y-V-L-A-N-W-M-NH2(SEQ ID NO: 524), X1-G-I-V-L-A-N-W-M-NH2(SEQ ID NO: 531 ),

[0768] X1-G-l-A6-L-A-N-W-V (SEQ ID NO: 117), X1-G-Y-A6-L-A-N-W-V (SEQ ID NO: 118), X1-G-A5-S-L-A-N-W-V (SEQ ID NO: 119), X1-G-A5-T-L-A-N-W-V (SEQ ID NO: 120), X1-G-A5-C-L-A-N-W-V (SEQ ID NO: 532),

[0769] GAR-P04562WO16 Application (final) docx X1-G-A5-N-L-A-N-W-V (SEQ ID NO: 533), X1-G-A5-Q-L-A-N-W-V (SEQ ID NO: 534), X1-G-A5-Y-L-A-N-W-V (SEQ ID NO: 535), X1-G-A5-A-L-A-N-W-V (SEQ ID NO: 536), X1-G-A5-G-L-A-N-W-V (SEQ ID NO: 537), X1-G-A5-V-L-A-N-W-V (SEQ ID NO: 538),

[0770] X1-A4-l-S-L-A-N-W-V (SEQ ID NO: 121 ), X1-A4-l-T-L-A-N-W-V (SEQ ID NO: 122), X1-A4-l-C-L-A-N-W-V (SEQ ID NO: 539), X1-A4-l-N-L-A-N-W-V (SEQ ID NO: 540), X1-A4-l-Q-L-A-N-W-V (SEQ ID NO: 541 ), X1-A4-l-Y-L-A-N-W-V (SEQ ID NO: 542), X1-A4-l-A-L-A-N-W-V (SEQ ID NO: 543), X1-A4-l-G-L-A-N-W-V (SEQ ID NO: 544), X1-A4-l-V-L-A-N-W-V (SEQ ID NO: 545),

[0771] X1-A4-Y-S-L-A-N-W-V (SEQ ID NO: 123), X1-A4-Y-T-L-A-N-W-V (SEQ ID NO: 124), X1-A4-Y-C-L-A-N-W-V (SEQ ID NO: 546), X1-A4-Y-N-L-A-N-W-V (SEQ ID NO: 547), X1-A4-Y-Q-L-A-N-W-V (SEQ ID NO: 548), X1-A4-Y-Y-L-A-N-W-V (SEQ ID NO: 549), X1-A4-Y-A-L-A-N-W-V (SEQ ID NO: 550), X1-A4-Y-G-L-A-N-W-V (SEQ ID NO: 551 ), X1-A4-Y-V-L-A-N-W-V (SEQ ID NO: 552),

[0772] X1-G-Y-S-L-A-N-W-V (SEQ ID NO: 125), X1-G-l-S-L-A-N-W-V (SEQ ID NO: 126), X1-G-Y-T-L-A-N-W-V (SEQ ID NO: 127), X1-G-l-T-L-A-N-W-V (SEQ ID NO: 128), X1-G-Y-C-L-A-N-W-V (SEQ ID NO: 553), X1-G-l-C-L-A-N-W-V (SEQ ID NO: 560), X1-G-Y-N-L-A-N-W-V (SEQ ID NO: 554), X1-G-l-N-L-A-N-W-V (SEQ ID NO: 561), X1-G-Y-Q-L-A-N-W-V (SEQ ID NO: 555), X1-G-l-Q-L-A-N-W-V (SEQ ID NO: 562), X1-G-Y-Y-L-A-N-W-V (SEQ ID NO: 556),

[0773] GAR-P04562WO16 Application (final) docx ABK "

[0774] 50

[0775] X1-G-Y-Y-L-A-N-W-V (SEQ ID NO: 563), X1-G-Y-A-L-A-N-W-V (SEQ ID NO: 557), X1-G-Y-A-L-A-N-W-V (SEQ ID NO: 564), X1-G-Y-G-L-A-N-W-V (SEQ ID NO: 558), X1-G-Y-G-L-A-N-W-V (SEQ ID NO: 565), X1-G-Y-V-L-A-N-W-V (SEQ ID NO: 559), X1-G-Y-V-L-A-N-W-V (SEQ ID NO: 566),

[0776] X4-R-G-l-A6-X2, X4-R-G-Y-A6-X2, X4-R-G-A5-S-X2, X4-R-G-A5-T-X2, X4-R-G-A5-C-X2, X4-R-G-A5-N-X2, X4-R-G-A5-Q-X2, X4-R-G-A5-Y-X2, X4-R-G-A5-A-X2, X4-R-G-A5-G-X2, X4-R-G-A5-V-X2, X4-R-A4-l-S-X2, X4-R-A4-l-T-X2, X4-R-A4-l-C-X2, X4-R-A4-l-N-X2, X4-R-A4-l-Q-X2, X4-R-A4-l-Y-X2, X4-R-A4-l-A-X2, X4-R-A4-l-G-X2, X4-R-A4-l-V-X2, X4-R-A4-Y-S-X2, X4-R-A4-Y-T-X2, X4-R-A4-Y-C-X2, X4-R-A4-Y-N-X2, X4-R-A4-Y-Q-X2, X4-R-A4-Y-Y-X2, X4-R-A4-Y-A-X2, X4-R-A4-Y-G-X2, X4-R-A4-Y-V-X2,

[0777] GAR-P04562WO16 Application (final) docx X4-R-G-Y-S-X2(SEQ ID NO: 129), X4-R-G-l-S-X2(SEQ ID NO: 130), X4-R-G-Y-T-X2(SEQ ID NO: 131 ), X4-R-G-l-T-X2(SEQ ID NO: 132), X4-R-G-Y-C-X2(SEQ ID NO: 567), X4-R-G-l-C-X2(SEQ ID NO: 574), X4-R-G-Y-N-X2(SEQ ID NO: 568), X4-R-G-l-N-X2(SEQ ID NO: 575), X4-R-G-Y-Q-X2(SEQ ID NO: 569), X4-R-G-l-Q-X2(SEQ ID NO: 576), X4-R-G-Y-Y-X2(SEQ ID NO: 570), X4-R-G-l-Y-X2(SEQ ID NO: 577), X4-R-G-Y-A-X2(SEQ ID NO: 571 ), X4-R-G-l-A-X2(SEQ ID NO: 578), X4-R-G-Y-G-X2(SEQ ID NO: 572), X4-R-G-l-G-X2(SEQ ID NO: 579), X4-R-G-Y-V-X2(SEQ ID NO: 573), X4-R-G-l-V-X2(SEQ ID NO: 580),

[0778] X4-K-G-l-A6-X2, X4-K-G-Y-A6-X2, X4-K-G-A5-S-X2, X4-K-G-A5-T-X2, X4-K-G-A5-C-X2, X4-K-G-A5-N-X2, X4-K-G-A5-Q-X2, X4-K-G-A5-Y-X2, X4-K-G-A5-A-X2, X4-K-G-A5-G-X2, X4-K-G-A5-V-X2, X4-K-A4-l-S-X2, X4-K-A4-l-T-X2, X4-K-A4-l-C-X2, X4-K-A4-l-N-X2, X4-K-A4-l-Q-X2, X4-K-A4-l-Y-X2, X4-K-A4-l-A-X2,

[0779] GAR-P04562WO16 Application (final) docx X4-K-A4-l-G-X2X4-K-A4-l-V-X2X4-K-A4-Y-S-X2X4-K-A4-Y-T-X2X4-K-A4-Y-C-X2X4-K-A4-Y-N-X2X4-K-A4-Y-Q-X2X4-K-A4-Y-Y-X2X4-K-A4-Y-A-X2X4-K-A4-Y-G-X2, X4-K-A4-Y-V-X2,

[0780] X4-K-G-Y-S-X2(SEQ ID NO: 133), X4-K-G-l-S-X2(SEQ ID NO: 134), X4-K-G-Y-T-X2(SEQ ID NO: 135), X4-K-G-l-T-X2(SEQ ID NO: 136), X4-K-G-Y-C-X2(SEQ ID NO: 581 ), X4-K-G-l-C-X2(SEQ ID NO: 588), X4-K-G-Y-N-X2(SEQ ID NO: 582), X4-K-G-l-N-X2(SEQ ID NO: 589), X4-K-G-Y-Q-X2(SEQ ID NO: 583), X4-K-G-l-Q-X2(SEQ ID NO: 590), X4-K-G-Y-Y-X2(SEQ ID NO: 584), X4-K-G-l-Y-X2(SEQ ID NO: 591 ), X4-K-G-Y-A-X2(SEQ ID NO: 585), X4-K-G-l-A-X2(SEQ ID NO: 592), X4-K-G-Y-G-X2(SEQ ID NO: 586), X4-K-G-l-G-X2(SEQ ID NO: 593), X4-K-G-Y-V-X2(SEQ ID NO: 587), X4-K-G-l-V-X2(SEQ ID NO: 594),

[0781] X4-L-G-l-A6-X2, X4-L-G-Y-A6-X2, X4-L-G-A5-S-X2, X4-L-G-A5-T-X2, X4-L-G-A5-C-X2, X4-L-G-A5-N-X2, X4-L-G-A5-Q-X2,

[0782] GAR-P04562WO16 Application (final) docx X4-L-G-A5-Y-X2, X4-L-G-A5-A-X2, X4-L-G-A5-G-X2, X4-L-G-A5-V-X2, X4-L-A4-l-S-X2, X4-L-A4-l-T-X2, X4-L-A4-l-C-X2, X4-L-A4-I-N-X2, X4-L-A4-l-Q-X2, X4-L-A4-l-Y-X2, X4-L-A4-l-A-X2, X4-L-A4-l-G-X2, X4-L-A4-l-V-X2, X4-L-A4-Y-S-X2, X4-L-A4-Y-T-X2, X4-L-A4-Y-C-X2, X4-L-A4-Y-N-X2, X4-L-A4-Y-Q-X2, X4-L-A4-Y-Y-X2, X4-L-A4-Y-A-X2, X4-L-A4-Y-G-X2, X4-L-A4-Y-V-X2,

[0783] X4-L-G-Y-S-X2(SEQ ID NO: 137), X4-L-G-l-S-X2(SEQ ID NO: 138), X4-L-G-Y-T-X2(SEQ ID NO: 139), X4-L-G-l-T-X2(SEQ ID NO: 140), X4-L-G-Y-C-X2(SEQ ID NO: 595), X4-L-G-l-C-X2(SEQ ID NO: 602), X4-L-G-Y-N-X2(SEQ ID NO: 596), X4-L-G-l-N-X2(SEQ ID NO: 603), X4-L-G-Y-Q-X2(SEQ ID NO: 597), X4-L-G-l-Q-X2(SEQ ID NO: 604), X4-L-G-Y-Y-X2(SEQ ID NO: 598), X4-L-G-l-Y-X2(SEQ ID NO: 605), X4-L-G-Y-A-X2(SEQ ID NO: 599), X4-L-G-l-A-X2(SEQ ID NO: 606), X4-L-G-Y-G-X2(SEQ ID NO: 600),

[0784] GAR-P04562WO16 Application (final) docx X4-L-G-l-G-X2(SEQ ID NO: 607), X4-L-G-Y-V-X2(SEQ ID NO: 601 ), X4-L-G-l-V-X2(SEQ ID NO: 608),

[0785] X6-Y-R-G-l-A6-X2(SEQ ID NO: 141 ), X6-Y-R-G-Y-A6-X2(SEQ ID NO: 142), X6-Y-R-G-A5-S-X2(SEQ ID NO: 143), X6-Y-R-G-A5-T-X2(SEQ ID NO: 144), X6-Y-R-G-A5-C-X2(SEQ ID NO: 609), X6-Y-R-G-A5-N-X2(SEQ ID NO: 610), X6-Y-R-G-A5-Q-X2(SEQ ID NO: 611 ), X6-Y-R-G-A5-Y-X2(SEQ ID NO: 612), X6-Y-R-G-A5-A-X2(SEQ ID NO: 613), X6-Y-R-G-A5-G-X2(SEQ ID NO: 614), X6-Y-R-G-A5-V-X2(SEQ ID NO: 615),

[0786] X6-Y-R-A4-l-S-X2(SEQ ID NO: 145), X6-Y-R-A4-l-T-X2(SEQ ID NO: 146), X6-Y-R-A4-l-C-X2(SEQ ID NO: 616), X6-Y-R-A4-l-N-X2(SEQ ID NO: 617), X6-Y-R-A4-l-Q-X2(SEQ ID NO: 618), X6-Y-R-A4-l-Y-X2(SEQ ID NO: 619), X6-Y-R-A4-l-A-X2(SEQ ID NO: 620), X6-Y-R-A4-l-G-X2(SEQ ID NO: 621 ), X6-Y-R-A4-l-V-X2(SEQ ID NO: 622),

[0787] X6-Y-R-A4-Y-S-X2(SEQ ID NO: 147), X6-Y-R-A4-Y-T-X2, (SEQ ID NO: 148), X6-Y-R-A4-Y-C-X2(SEQ ID NO: 623), X6-Y-R-A4-Y-N-X2, (SEQ ID NO: 624), X6-Y-R-A4-Y-Q-X2(SEQ ID NO: 625), X6-Y-R-A4-Y-Y-X2, (SEQ ID NO: 626), X6-Y-R-A4-Y-A-X2(SEQ ID NO: 627), X6-Y-R-A4-Y-G-X2, (SEQ ID NO: 628), X6-Y-R-A4-Y-V-X2(SEQ ID NO: 629),

[0788] X6-Y-R-G-Y-S-X2(SEQ ID NO: 149), X6-Y-R-G-l-S-X2(SEQ ID NO: 150),

[0789] GAR-P04562WO16 Application (final) docx X6-Y-R-G-Y-T-X2(SEQ ID NO: 151 ), X6-Y-R-G-l-T-X2(SEQ ID NO: 152), X6-Y-R-G-Y-C-X2(SEQ ID NO: 630), X6-Y-R-G-l-C-X2(SEQ ID NO: 637), X6-Y-R-G-Y-N-X2(SEQ ID NO: 631 ), X6-Y-R-G-l-N-X2(SEQ ID NO: 638), X6-Y-R-G-Y-Q-X2(SEQ ID NO: 632), X6-Y-R-G-l-Q-X2(SEQ ID NO: 639), X6-Y-R-G-Y-Y-X2(SEQ ID NO: 633), X6-Y-R-G-l-Y-X2(SEQ ID NO: 640), X6-Y-R-G-Y-A-X2(SEQ ID NO: 634), X6-Y-R-G-l-A-X2(SEQ ID NO: 641 ), X6-Y-R-G-Y-G-X2(SEQ ID NO: 635), X6-Y-R-G-l-G-X2(SEQ ID NO: 642), X6-Y-R-G-Y-V-X2(SEQ ID NO: 636), X6-Y-R-G-l-V-X2(SEQ ID NO: 643),

[0790] X6-Y-K-G-l-A6-X2(SEQ ID NO: 153), X6-Y-K-G-Y-A6-X2(SEQ ID NO: 154), X6-Y-K-G-A5-S-X2(SEQ ID NO: 155), X6-Y-K-G-A5-T-X2(SEQ ID NO: 156), X6-Y-K-G-A5-C-X2(SEQ ID NO: 644), X6-Y-K-G-A5-N-X2(SEQ ID NO: 645), X6-Y-K-G-A5-Q-X2(SEQ ID NO: 646), X6-Y-K-G-A5-Y-X2(SEQ ID NO: 647), X6-Y-K-G-A5-A-X2(SEQ ID NO: 648), X6-Y-K-G-A5-G-X2(SEQ ID NO: 649), X6-Y-K-G-A5-V-X2(SEQ ID NO: 650),

[0791] X6-Y-K-A4-l-S-X2(SEQ ID NO: 157), X6-Y-K-A4-l-T-X2(SEQ ID NO: 158), X6-Y-K-A4-l-C-X2(SEQ ID NO: 651 ), X6-Y-K-A4-l-N-X2(SEQ ID NO: 652), X6-Y-K-A4-l-Q-X2(SEQ ID NO: 653), X6-Y-K-A4-l-Y-X2(SEQ ID NO: 654), X6-Y-K-A4-l-A-X2(SEQ ID NO: 655), X6-Y-K-A4-l-G-X2(SEQ ID NO: 656), X6-Y-K-A4-l-V-X2(SEQ ID NO: 657),

[0792] GAR-P04562WO16 Application (final) docx X6-Y-K-A4-Y-S-X2(SEQ ID NO: 159), X6-Y-K-A4-Y-T-X2(SEQ ID NO: 160), X6-Y-K-A4-Y-C-X2(SEQ ID NO: 658), X6-Y-K-A4-Y-N-X2(SEQ ID NO: 659), X6-Y-K-A4-Y-Q-X2(SEQ ID NO: 660), X6-Y-K-A4-Y-Y-X2(SEQ ID NO: 661 ), X6-Y-K-A4-Y-A-X2(SEQ ID NO: 662), X6-Y-K-A4-Y-G-X2(SEQ ID NO: 663), X6-Y-K-A4-Y-V-X2(SEQ ID NO: 664),

[0793] X6-Y-K-G-Y-S-X2(SEQ ID NO: 161 ), X6-Y-K-G-l-S-X2(SEQ ID NO: 162), X6-Y-K-G-Y-T-X2(SEQ ID NO: 163), X6-Y-K-G-l-T-X2(SEQ ID NO: 164), X6-Y-K-G-Y-C-X2(SEQ ID NO: 665), X6-Y-K-G-l-C-X2(SEQ ID NO: 672), X6-Y-K-G-Y-N-X2(SEQ ID NO: 666), X6-Y-K-G-l-N-X2(SEQ ID NO: 673), X6-Y-K-G-Y-Q-X2(SEQ ID NO: 667), X6-Y-K-G-l-Q-X2(SEQ ID NO: 674), X6-Y-K-G-Y-Y-X2(SEQ ID NO: 668), X6-Y-K-G-l-Y-X2(SEQ ID NO: 675), X6-Y-K-G-Y-A-X2(SEQ ID NO: 669), X6-Y-K-G-l-A-X2(SEQ ID NO: 676), X6-Y-K-G-Y-G-X2(SEQ ID NO: 670), X6-Y-K-G-l-G-X2(SEQ ID NO: 677), X6-Y-K-G-Y-V-X2(SEQ ID NO: 671 ), X6-Y-K-G-l-V-X2(SEQ ID NO: 678),

[0794] X6-Y-L-G-l-A6-X2(SEQ ID NO: 165), X6-Y-L-G-Y-A6-X2(SEQ ID NO: 166), X6-Y-L-G-A5-S-X2(SEQ ID NO: 167), X6-Y-L-G-A5-T-X2(SEQ ID NO: 168), X6-Y-L-G-A5-C-X2(SEQ ID NO: 679), X6-Y-L-G-A5-N-X2(SEQ ID NO: 680), X6-Y-L-G-A5-Q-X2(SEQ ID NO: 681 ), X6-Y-L-G-A5-Y-X2(SEQ ID NO: 682),

[0795] GAR-P04562WO16 Application (final) docx X6-Y-L-G-A5-A-X2(SEQ ID NO: 683), X6-Y-L-G-A5-G-X2(SEQ ID NO: 684), X6-Y-L-G-A5-V-X2(SEQ ID NO: 685),

[0796] X6-Y-L-A4-l-S-X2(SEQ ID NO: 169), X6-Y-L-A4-l-T-X2(SEQ ID NO: 170), X6-Y-L-A4-l-C-X2(SEQ ID NO: 686), X6-Y-L-A4-l-N-X2(SEQ ID NO: 687), X6-Y-L-A4-l-Q-X2(SEQ ID NO: 688), X6-Y-L-A4-l-Y-X2(SEQ ID NO: 689), X6-Y-L-A4-l-A-X2(SEQ ID NO: 690), X6-Y-L-A4-l-G-X2(SEQ ID NO: 691 ), X6-Y-L-A4-l-V-X2(SEQ ID NO: 692),

[0797] X6-Y-L-A4-Y-S-X2(SEQ ID NO: 171 ), X6-Y-L-A4-Y-T-X2(SEQ ID NO: 172), X6-Y-L-A4-Y-C-X2(SEQ ID NO: 693), X6-Y-L-A4-Y-N-X2(SEQ ID NO: 694), X6-Y-L-A4-Y-Q-X2(SEQ ID NO: 695), X6-Y-L-A4-Y-Y-X2(SEQ ID NO: 696), X6-Y-L-A4-Y-A-X2(SEQ ID NO: 697), X6-Y-L-A4-Y-G-X2(SEQ ID NO: 698), X6-Y-L-A4-Y-V-X2(SEQ ID NO: 699),

[0798] X6-Y-L-G-Y-S-X2(SEQ ID NO: 173), X6-Y-L-G-l-S-X2(SEQ ID NO: 174), X6-Y-L-G-Y-T-X2(SEQ ID NO: 175), X6-Y-L-G-l-T-X2(SEQ ID NO: 176), X6-Y-L-G-Y-C-X2(SEQ ID NO: 700), X6-Y-L-G-l-C-X2(SEQ ID NO: 707), X6-Y-L-G-Y-N-X2(SEQ ID NO: 701 ), X6-Y-L-G-l-N-X2(SEQ ID NO: 708), X6-Y-L-G-Y-Q-X2(SEQ ID NO: 702), X6-Y-L-G-l-Q-X2(SEQ ID NO: 709), X6-Y-L-G-Y-Y-X2(SEQ ID NO: 703), X6-Y-L-G-l-Y-X2(SEQ ID NO: 710), X6-Y-L-G-Y-A-X2(SEQ ID NO: 704), X6-Y-L-G-l-A-X2(SEQ ID NO: 711 ),

[0799] GAR-P04562WO16 Application (final) docx -ABK

[0800] 58

[0801] X6-Y-L-G-Y-G-X2(SEQ ID NO: 705), X6-Y-L-G-l-G-X2(SEQ ID NO: 712), X6-Y-L-G-Y-V-X2(SEQ ID NO: 706), X6-Y-L-G-l-V-X2(SEQ ID NO: 713),

[0802] X6-F-R-G-l-A6-X2(SEQ ID NO: 177), X6-F-R-G-Y-A6-X2(SEQ ID NO: 178),

[0803] X6-F-R-G-A5-S-X2(SEQ ID NO: 179), X6-F-R-G-A5-T-X2(SEQ ID NO: 180), X6-F-R-G-A5-C-X2(SEQ ID NO: 714), X6-F-R-G-A5-N-X2(SEQ ID NO: 715), X6-F-R-G-A5-Q-X2(SEQ ID NO: 716), X6-F-R-G-A5-Y-X2(SEQ ID NO: 717), X6-F-R-G-A5-A-X2(SEQ ID NO: 718), X6-F-R-G-A5-G-X2(SEQ ID NO: 719), X6-F-R-G-A5-V-X2(SEQ ID NO: 720),

[0804] X6-F-R-A4-l-S-X2(SEQ ID NO: 181 ), X6-F-R-A4-l-T-X2(SEQ ID NO: 182), X6-F-R-A4-l-C-X2(SEQ ID NO: 721 ), X6-F-R-A4-l-N-X2(SEQ ID NO: 722), X6-F-R-A4-l-Q-X2(SEQ ID NO: 723), X6-F-R-A4-l-Y-X2(SEQ ID NO: 724), X6-F-R-A4-l-A-X2(SEQ ID NO: 725), X6-F-R-A4-l-G-X2(SEQ ID NO: 726), X6-F-R-A4-l-V-X2(SEQ ID NO: 727),

[0805] X6-F-R-A4-Y-S-X2(SEQ ID NO: 183), X6-F-R-A4-Y-T-X2(SEQ ID NO: 184), X6-F-R-A4-Y-C-X2(SEQ ID NO: 728), X6-F-R-A4-Y-N-X2(SEQ ID NO: 729), X6-F-R-A4-Y-Q-X2(SEQ ID NO: 730), X6-F-R-A4-Y-Y-X2(SEQ ID NO: 731 ), X6-F-R-A4-Y-A-X2(SEQ ID NO: 732), X6-F-R-A4-Y-G-X2(SEQ ID NO: 733), X6-F-R-A4-Y-V-X2(SEQ ID NO: 734),

[0806] GAR-P04562WO16 Application (final) docx X6-F-R-G-Y-S-X2(SEQ ID NO: 185), X6-F-R-G-l-S-X2(SEQ ID NO: 186), X6-F-R-G-Y-T-X2(SEQ ID NO: 187), X6-F-R-G-l-T-X2(SEQ ID NO: 188), X6-F-R-G-Y-C-X2(SEQ ID NO: 735), X6-F-R-G-l-C-X2(SEQ ID NO: 742), X6-F-R-G-Y-N-X2(SEQ ID NO: 736), X6-F-R-G-l-N-X2(SEQ ID NO: 743), X6-F-R-G-Y-Q-X2(SEQ ID NO: 737), X6-F-R-G-l-Q-X2(SEQ ID NO: 744), X6-F-R-G-Y-Y-X2(SEQ ID NO: 738), X6-F-R-G-l-Y-X2(SEQ ID NO: 745), X6-F-R-G-Y-A-X2(SEQ ID NO: 739), X6-F-R-G-l-A-X2(SEQ ID NO: 746), X6-F-R-G-Y-G-X2(SEQ ID NO: 740), X6-F-R-G-l-G-X2(SEQ ID NO: 747), X6-F-R-G-Y-V-X2(SEQ ID NO: 741 ), X6-F-R-G-l-V-X2(SEQ ID NO: 748),

[0807] X6-F-K-G-l-A6-X2(SEQ ID NO: 189), X6-F-K-G-Y-A6-X2(SEQ ID NO: 190), X6-F-K-G-A5-S-X2(SEQ ID NO: 191 ), X6-F-K-G-A5-T-X2(SEQ ID NO: 192), X6-F-K-G-A5-C-X2(SEQ ID NO: 749); X6-F-K-G-A5-N-X2(SEQ ID NO: 750), X6-F-K-G-A5-Q-X2(SEQ ID NO: 751 ), X6-F-K-G-A5-Y-X2(SEQ ID NO: 752), X6-F-K-G-A5-A-X2(SEQ ID NO: 753), X6-F-K-G-A5-G-X2(SEQ ID NO: 754), X6-F-K-G-A5-V-X2(SEQ ID NO: 755),

[0808] X6-F-K-A4-l-S-X2(SEQ ID NO: 193), X6-F-K-A4-l-T-X2(SEQ ID NO: 194), X6-F-K-A4-l-C-X2(SEQ ID NO: 756), X6-F-K-A4-l-N-X2(SEQ ID NO: 757), X6-F-K-A4-l-Q-X2(SEQ ID NO: 758), X6-F-K-A4-l-Y-X2(SEQ ID NO: 759), X6-F-K-A4-l-A-X2(SEQ ID NO: 760),

[0809] GAR-P04562WO16 Application (final) docx X6-F-K-A4-l-G-X2(SEQ ID NO: 761 ), X6-F-K-A4-l-V-X2(SEQ ID NO: 762),

[0810] X6-F-K-A4-Y-S-X2(SEQ ID NO: 195), X6-F-K-A4-Y-T-X2(SEQ ID NO: 196), X6-F-K-A4-Y-C-X2(SEQ ID NO: 763), X6-F-K-A4-Y-N-X2(SEQ ID NO: 764), X6-F-K-A4-Y-Q-X2(SEQ ID NO: 765), X6-F-K-A4-Y-Y-X2(SEQ ID NO: 766), X6-F-K-A4-Y-A-X2(SEQ ID NO: 767), X6-F-K-A4-Y-G-X2(SEQ ID NO: 768), X6-F-K-A4-Y-V-X2(SEQ ID NO: 769),

[0811] X6-F-K-G-Y-S-X2(SEQ ID NO: 197), X6-F-K-G-l-S-X2(SEQ ID NO: 198), X6-F-K-G-Y-T-X2(SEQ ID NO: 199), X6-F-K-G-l-T-X2(SEQ ID NO: 200), X6-F-K-G-Y-C-X2(SEQ ID NO: 770), X6-F-K-G-l-C-X2(SEQ ID NO: 777), X6-F-K-G-Y-N-X2(SEQ ID NO: 771 ), X6-F-K-G-l-N-X2(SEQ ID NO: 778), X6-F-K-G-Y-Q-X2(SEQ ID NO: 772), X6-F-K-G-l-Q-X2(SEQ ID NO: 779), X6-F-K-G-Y-Y-X2(SEQ ID NO: 773), X6-F-K-G-l-Y-X2(SEQ ID NO: 780), X6-F-K-G-Y-A-X2(SEQ ID NO: 774), X6-F-K-G-l-A-X2(SEQ ID NO: 781 ), X6-F-K-G-Y-G-X2(SEQ ID NO: 775), X6-F-K-G-l-G-X2(SEQ ID NO: 782), X6-F-K-G-Y-V-X2(SEQ ID NO: 776), X6-F-K-G-l-V-X2(SEQ ID NO: 783),

[0812] X6-F-L-G-l-A6-X2(SEQ ID NO: 310), X6-F-L-G-Y-A6-X2(SEQ ID NO: 201 ), X6-F-L-G-A5-S-X2(SEQ ID NO: 202), X6-F-L-G-A5-T-X2(SEQ ID NO: 203), X6-F-L-G-A5-C-X2(SEQ ID NO: 784), X6-F-L-G-A5-N-X2(SEQ ID NO: 785),

[0813] GAR-P04562WO16 Application (final) docx X6-F-L-G-A5-Q-X2(SEQ ID NO: 786), X6-F-L-G-A5-Y-X2(SEQ ID NO: 787), X6-F-L-G-A5-A-X2(SEQ ID NO: 788), X6-F-L-G-A5-G-X2(SEQ ID NO: 789), X6-F-L-G-A5-V-X2(SEQ ID NO: 790),

[0814] X6-F-L-A4-l-S-X2(SEQ ID NO: 204), X6-F-L-A4-l-T-X2(SEQ ID NO: 205), X6-F-L-A4-l-C-X2(SEQ ID NO: 791 ), X6-F-L-A4-l-N-X2(SEQ ID NO: 792), X6-F-L-A4-l-Q-X2(SEQ ID NO: 793), X6-F-L-A4-l-Y-X2(SEQ ID NO: 794), X6-F-L-A4-l-A-X2(SEQ ID NO: 795), X6-F-L-A4-l-G-X2(SEQ ID NO: 796), X6-F-L-A4-l-V-X2(SEQ ID NO: 797),

[0815] X6-F-L-A4-Y-S-X2(SEQ ID NO: 206), X6-F-L-A4-Y-T-X2(SEQ ID NO: 207), X6-F-L-A4-Y-C-X2(SEQ ID NO: 798), X6-F-L-A4-Y-N-X2(SEQ ID NO: 799), X6-F-L-A4-Y-Q-X2(SEQ ID NO: 800), X6-F-L-A4-Y-Y-X2(SEQ ID NO: 801 ), X6-F-L-A4-Y-A-X2(SEQ ID NO: 802), X6-F-L-A4-Y-G-X2(SEQ ID NO: 803), X6-F-L-A4-Y-V-X2(SEQ ID NO: 804),

[0816] X6-F-L-G-Y-S-X2(SEQ ID NO: 208), X6-F-L-G-l-S-X2(SEQ ID NO: 209), X6-F-L-G-Y-T-X2(SEQ ID NO: 210), X6-F-L-G-l-T-X2(SEQ ID NO: 211 ), X6-F-L-G-Y-C-X2(SEQ ID NO: 805), X6-F-L-G-l-C-X2(SEQ ID NO: 812), X6-F-L-G-Y-N-X2(SEQ ID NO: 806), X6-F-L-G-l-N-X2(SEQ ID NO: 813), X6-F-L-G-Y-Q-X2(SEQ ID NO: 807), X6-F-L-G-l-Q-X2(SEQ ID NO: 814), X6-F-L-G-Y-Y-X2(SEQ ID NO: 808), X6-F-L-G-l-Y-X2(SEQ ID NO: 815),

[0817] GAR-P04562WO16 Application (final) docx -ABK

[0818] 62

[0819] X6-F-L-G-Y-A-X2(SEQ ID NO: 809), X6-F-L-G-l-A-X2(SEQ ID NO: 816), X6-F-L-G-Y-G-X2(SEQ ID NO: 810), X6-F-L-G-l-G-X2(SEQ ID NO: 817), X6-F-L-G-Y-V-X2(SEQ ID NO: 811 ), X6-F-L-G-l-V-X2(SEQ ID NO: 818),

[0820] G-Y-R-G-l-A6-X2(SEQ ID NO: 212), G-Y-R-G-Y-A6-X2(SEQ ID NO: 213), G-Y-R-G-A5-S-X2(SEQ ID NO: 214), G-Y-R-G-A5-T-X2(SEQ ID NO: 215), G-Y-R-G-A5-C-X2(SEQ ID NO: 819), G-Y-R-G-A5-N-X2(SEQ ID NO: 820), G-Y-R-G-A5-Q-X2(SEQ ID NO: 821 ), G-Y-R-G-A5-Y-X2(SEQ ID NO: 822), G-Y-R-G-A5-A-X2(SEQ ID NO: 823), G-Y-R-G-A5-G-X2(SEQ ID NO: 824), G-Y-R-G-A5-V-X2(SEQ ID NO: 825),

[0821] G-Y-R-A4-l-S-X2(SEQ ID NO: 216), G-Y-R-A4-l-T-X2(SEQ ID NO: 217), G-Y-R-A4-l-C-X2(SEQ ID NO: 826), G-Y-R-A4-l-N-X2(SEQ ID NO: 827), G-Y-R-A4-l-Q-X2(SEQ ID NO: 828), G-Y-R-A4-l-Y-X2(SEQ ID NO: 829), G-Y-R-A4-l-A-X2(SEQ ID NO: 830), G-Y-R-A4-l-G-X2(SEQ ID NO: 831 ), G-Y-R-A4-l-V-X2(SEQ ID NO: 832),

[0822] G-Y-R-A4-Y-S-X2(SEQ ID NO: 218), G-Y-R-A4-Y-T-X2(SEQ ID NO: 219), G-Y-R-A4-Y-C-X2(SEQ ID NO: 833), G-Y-R-A4-Y-N-X2(SEQ ID NO: 834), G-Y-R-A4-Y-Q-X2(SEQ ID NO: 835), G-Y-R-A4-Y-Y-X2(SEQ ID NO: 836), G-Y-R-A4-Y-A-X2(SEQ ID NO: 837), G-Y-R-A4-Y-G-X2(SEQ ID NO: 838), G-Y-R-A4-Y-V-X2(SEQ ID NO: 839),

[0823] GAR-P04562WO16 Application (final) docx G-Y-R-G-Y-S-X2(SEQ ID NO: 220), G-Y-R-G-l-S-X2(SEQ ID NO: 221 ), G-Y-R-G-Y-T-X2(SEQ ID NO: 222), G-Y-R-G-l-T-X2(SEQ ID NO: 223), G-Y-R-G-Y-C-X2(SEQ ID NO: 840), G-Y-R-G-l-C-X2(SEQ ID NO: 847), G-Y-R-G-Y-N-X2(SEQ ID NO: 841 ), G-Y-R-G-l-N-X2(SEQ ID NO: 848), G-Y-R-G-Y-Q-X2(SEQ ID NO: 842), G-Y-R-G-l-Q-X2(SEQ ID NO: 849), G-Y-R-G-Y-Y-X2(SEQ ID NO: 843), G-Y-R-G-l-Y-X2(SEQ ID NO: 850), G-Y-R-G-Y-A-X2(SEQ ID NO: 844), G-Y-R-G-l-A-X2(SEQ ID NO: 851 ), G-Y-R-G-Y-G-X2(SEQ ID NO: 845), G-Y-R-G-l-G-X2(SEQ ID NO: 852), G-Y-R-G-Y-V-X2(SEQ ID NO: 846), G-Y-R-G-l-V-X2(SEQ ID NO: 853),

[0824] G-Y-K-G-l-A6-X2(SEQ ID NO: 224), G-Y-K-G-Y-A6-X2(SEQ ID NO: 225), G-Y-K-G-A5-S-X2(SEQ ID NO: 226), G-Y-K-G-A5-T-X2(SEQ ID NO: 227), G-Y-K-G-A5-C-X2(SEQ ID NO: 854), G-Y-K-G-A5-N-X2(SEQ ID NO: 855), G-Y-K-G-A5-Q-X2(SEQ ID NO: 856), G-Y-K-G-A5-Y-X2(SEQ ID NO: 857), G-Y-K-G-A5-A-X2(SEQ ID NO: 858), G-Y-K-G-A5-G-X2(SEQ ID NO: 859), G-Y-K-G-A5-V-X2(SEQ ID NO: 860),

[0825] G-Y-K-A4-l-S-X2(SEQ ID NO: 228), G-Y-K-A4-l-T-X2(SEQ ID NO: 229), G-Y-K-A4-l-C-X2(SEQ ID NO: 861 ), G-Y-K-A4-l-N-X2(SEQ ID NO: 862), G-Y-K-A4-l-Q-X2(SEQ ID NO: 863), G-Y-K-A4-l-Y-X2(SEQ ID NO: 864),

[0826] GAR-P04562WO16 Application (final) docx -ABK

[0827] 64

[0828] G-Y-K-A4-l-A-X2(SEQ ID NO: 865), G-Y-K-A4-l-G-X2(SEQ ID NO: 866), G-Y-K-A4-l-V-X2(SEQ ID NO: 867),

[0829] G-Y-K-A4-Y-S-X2(SEQ ID NO: 230), G-Y-K-A4-Y-T-X2(SEQ ID NO: 231 ), G-Y-K-A4-Y-C-X2(SEQ ID NO: 868), G-Y-K-A4-Y-N-X2(SEQ ID NO: 869), G-Y-K-A4-Y-Q-X2(SEQ ID NO: 870), G-Y-K-A4-Y-Y-X2(SEQ ID NO: 871 ), G-Y-K-A4-Y-A-X2(SEQ ID NO: 872), G-Y-K-A4-Y-G-X2(SEQ ID NO: 873), G-Y-K-A4-Y-V-X2(SEQ ID NO: 874),

[0830] G-Y-K-G-Y-S-X2(SEQ ID NO: 232), G-Y-K-G-l-S-X2(SEQ ID NO: 233), G-Y-K-G-Y-T-X2(SEQ ID NO: 234), G-Y-K-G-l-T-X2(SEQ ID NO: 235), G-Y-K-G-Y-C-X2(SEQ ID NO: 875), G-Y-K-G-l-C-X2(SEQ ID NO: 882), G-Y-K-G-Y-N-X2(SEQ ID NO: 876), G-Y-K-G-l-N-X2(SEQ ID NO: 883), G-Y-K-G-Y-Q-X2(SEQ ID NO: 877), G-Y-K-G-l-Q-X2(SEQ ID NO: 884), G-Y-K-G-Y-Y-X2(SEQ ID NO: 878), G-Y-K-G-l-Y-X2(SEQ ID NO: 885), G-Y-K-G-Y-A-X2(SEQ ID NO: 879), G-Y-K-G-l-A-X2(SEQ ID NO: 886), G-Y-K-G-Y-G-X2(SEQ ID NO: 880), G-Y-K-G-l-G-X2(SEQ ID NO: 887), G-Y-K-G-Y-V-X2(SEQ ID NO: 881 ), G-Y-K-G-l-V-X2(SEQ ID NO: 888),

[0831] G-Y-L-G-l-A6-X2(SEQ ID NO: 236), G-Y-L-G-Y-A6-X2(SEQ ID NO: 237), G-Y-L-G-A5-S-X2(SEQ ID NO: 238), G-Y-L-G-A5-T-X2(SEQ ID NO: 239), G-Y-L-G-A5-C-X2(SEQ ID NO: 889),

[0832] GAR-P04562WO16 Application (final) docx G-Y-L-G-A5-N-X2(SEQ ID NO: 890), G-Y-L-G-A5-Q-X2(SEQ ID NO: 891 ), G-Y-L-G-A5-Y-X2(SEQ ID NO: 892), G-Y-L-G-A5-A-X2(SEQ ID NO: 893), G-Y-L-G-A5-G-X2(SEQ ID NO: 894), G-Y-L-G-A5-V-X2(SEQ ID NO: 895),

[0833] G-Y-L-A4-l-S-X2(SEQ ID NO: 240), G-Y-L-A4-l-T-X2(SEQ ID NO: 241 ), G-Y-L-A4-l-C-X2(SEQ ID NO: 896), G-Y-L-A4-l-N-X2(SEQ ID NO: 897), G-Y-L-A4-l-Q-X2(SEQ ID NO: 898), G-Y-L-A4-l-Y-X2(SEQ ID NO: 899), G-Y-L-A4-l-A-X2(SEQ ID NO: 900), G-Y-L-A4-l-G-X2(SEQ ID NO: 901 ), G-Y-L-A4-l-V-X2(SEQ ID NO: 902),

[0834] G-Y-L-A4-Y-S-X2(SEQ ID NO: 242), G-Y-L-A4-Y-T-X2(SEQ ID NO: 243), G-Y-L-A4-Y-C-X2(SEQ ID NO: 903), G-Y-L-A4-Y-N-X2(SEQ ID NO: 904), G-Y-L-A4-Y-Q-X2(SEQ ID NO: 905), G-Y-L-A4-Y-Y-X2(SEQ ID NO: 906), G-Y-L-A4-Y-A-X2(SEQ ID NO: 907), G-Y-L-A4-Y-G-X2(SEQ ID NO: 908), G-Y-L-A4-Y-V-X2(SEQ ID NO: 909),

[0835] G-Y-L-G-Y-S-X2(SEQ ID NO: 244), G-Y-L-G-l-S-X2(SEQ ID NO: 245), G-Y-L-G-Y-T-X2(SEQ ID NO: 246), G-Y-L-G-l-T-X2(SEQ ID NO: 247), G-Y-L-G-Y-C-X2(SEQ ID NO: 910), G-Y-L-G-l-C-X2(SEQ ID NO: 917), G-Y-L-G-Y-N-X2(SEQ ID NO: 911 ), G-Y-L-G-l-N-X2(SEQ ID NO: 918), G-Y-L-G-Y-Q-X2(SEQ ID NO: 912), G-Y-L-G-l-Q-X2(SEQ ID NO: 919), G-Y-L-G-Y-Y-X2(SEQ ID NO: 913),

[0836] GAR-P04562WO16 Application (final) docx G-Y-L-G-l-Y-X2(SEQ ID NO: 920), G-Y-L-G-Y-A-X2(SEQ ID NO: 914), G-Y-L-G-l-A-X2(SEQ ID NO: 921 ), G-Y-L-G-Y-G-X2(SEQ ID NO: 915), G-Y-L-G-l-G-X2(SEQ ID NO: 922), G-Y-L-G-Y-V-X2(SEQ ID NO: 916), G-Y-L-G-l-V-X2(SEQ ID NO: 923),

[0837] G-F-R-G-l-A6-X2(SEQ ID NO: 248), G-F-R-G-Y-A6-X2(SEQ ID NO: 249), G-F-R-G-A5-S-X2(SEQ ID NO: 250), G-F-R-G-A5-T-X2(SEQ ID NO: 251 ), G-F-R-G-A5-C-X2(SEQ ID NO: 924), G-F-R-G-A5-N-X2(SEQ ID NO: 925), G-F-R-G-A5-Q-X2(SEQ ID NO: 926), G-F-R-G-A5-Y-X2(SEQ ID NO: 927), G-F-R-G-A5-A-X2(SEQ ID NO: 928), G-F-R-G-A5-G-X2(SEQ ID NO: 929), G-F-R-G-A5-V-X2(SEQ ID NO: 930),

[0838] G-F-R-A4-l-S-X2(SEQ ID NO: 252), G-F-R-A4-l-T-X2(SEQ ID NO: 253), G-F-R-A4-l-C-X2(SEQ ID NO: 931 ), G-F-R-A4-l-N-X2(SEQ ID NO: 932), G-F-R-A4-l-Q-X2(SEQ ID NO: 933), G-F-R-A4-l-Y-X2(SEQ ID NO: 934), G-F-R-A4-l-A-X2(SEQ ID NO: 935), G-F-R-A4-l-G-X2(SEQ ID NO: 936), G-F-R-A4-l-V-X2(SEQ ID NO: 937),

[0839] G-F-R-A4-Y-S-X2(SEQ ID NO: 254), G-F-R-A4-Y-T-X2(SEQ ID NO: 255), G-F-R-A4-Y-C-X2(SEQ ID NO: 938), G-F-R-A4-Y-N-X2(SEQ ID NO: 939), G-F-R-A4-Y-Q-X2(SEQ ID NO: 940), G-F-R-A4-Y-Y-X2(SEQ ID NO: 941 ), G-F-R-A4-Y-A-X2(SEQ ID NO: 942), G-F-R-A4-Y-G-X2(SEQ ID NO: 943),

[0840] GAR-P04562WO16 Application (final) docx -ABK

[0841] 67

[0842] G-F-R-A4-Y-V-X2(SEQ ID NO: 944),

[0843] G-F-R-G-Y-S-X2(SEQ ID NO: 256), G-F-R-G-l-S-X2(SEQ ID NO: 257), G-F-R-G-Y-T-X2(SEQ ID NO: 258), G-F-R-G-l-T-X2(SEQ ID NO: 259), G-F-R-G-Y-C-X2(SEQ ID NO: 945), G-F-R-G-l-C-X2(SEQ ID NO: 952), G-F-R-G-Y-N-X2(SEQ ID NO: 946), G-F-R-G-l-N-X2(SEQ ID NO: 953), G-F-R-G-Y-Q-X2(SEQ ID NO: 947), G-F-R-G-l-Q-X2(SEQ ID NO: 954), G-F-R-G-Y-Y-X2(SEQ ID NO: 948), G-F-R-G-l-Y-X2(SEQ ID NO: 955), G-F-R-G-Y-A-X2(SEQ ID NO: 949), G-F-R-G-l-A-X2(SEQ ID NO: 956), G-F-R-G-Y-G-X2(SEQ ID NO: 950), G-F-R-G-l-G-X2(SEQ ID NO: 957), G-F-R-G-Y-V-X2(SEQ ID NO: 951 ), G-F-R-G-l-V-X2(SEQ ID NO: 958),

[0844] G-F-K-G-l-A6-X2(SEQ ID NO: 260), G-F-K-G-Y-A6-X2(SEQ ID NO: 261 ), G-F-K-G-A5-S-X2(SEQ ID NO: 262), G-F-K-G-A5-T-X2(SEQ ID NO: 263), G-F-K-G-A5-C-X2(SEQ ID NO: 959), G-F-K-G-A5-N-X2(SEQ ID NO: 960), G-F-K-G-A5-Q-X2(SEQ ID NO: 961 ), G-F-K-G-A5-Y-X2(SEQ ID NO: 962), G-F-K-G-A5-A-X2(SEQ ID NO: 963), G-F-K-G-A5-G-X2(SEQ ID NO: 964), G-F-K-G-A5-V-X2(SEQ ID NO: 965),

[0845] G-F-K-A4-l-S-X2(SEQ ID NO: 264), G-F-K-A4-l-T-X2(SEQ ID NO: 265), G-F-K-A4-l-C-X2(SEQ ID NO: 966), G-F-K-A4-l-N-X2(SEQ ID NO: 967), G-F-K-A4-l-Q-X2(SEQ ID NO: 968),

[0846] GAR-P04562WO16 Application (final) docx G-F-K-A4-l-Y-X2(SEQ ID NO: 969), G-F-K-A4-l-A-X2(SEQ ID NO: 970), G-F-K-A4-l-G-X2(SEQ ID NO: 971 ), G-F-K-A4-l-V-X2(SEQ ID NO: 972),

[0847] G-F-K-A4-Y-S-X2(SEQ ID NO: 266), G-F-K-A4-Y-T-X2(SEQ ID NO: 267), G-F-K-A4-Y-C-X2(SEQ ID NO: 973), G-F-K-A4-Y-N-X2(SEQ ID NO: 974), G-F-K-A4-Y-Q-X2(SEQ ID NO: 975), G-F-K-A4-Y-Y-X2(SEQ ID NO: 976), G-F-K-A4-Y-A-X2(SEQ ID NO: 977), G-F-K-A4-Y-G-X2(SEQ ID NO: 978), G-F-K-A4-Y-V-X2(SEQ ID NO: 979),

[0848] G-F-K-G-Y-S-X2(SEQ ID NO: 268), G-F-K-G-l-S-X2(SEQ ID NO: 269), G-F-K-G-Y-T-X2(SEQ ID NO: 270), G-F-K-G-l-T-X2(SEQ ID NO: 271 ), G-F-K-G-Y-C-X2(SEQ ID NO: 980), G-F-K-G-l-C-X2(SEQ ID NO: 987), G-F-K-G-Y-N-X2(SEQ ID NO: 981 ), G-F-K-G-l-N-X2(SEQ ID NO: 988), G-F-K-G-Y-Q-X2(SEQ ID NO: 982), G-F-K-G-l-Q-X2(SEQ ID NO: 989), G-F-K-G-Y-Y-X2(SEQ ID NO: 983), G-F-K-G-l-Y-X2(SEQ ID NO: 990), G-F-K-G-Y-A-X2(SEQ ID NO: 984), G-F-K-G-l-A-X2(SEQ ID NO: 991 ), G-F-K-G-Y-G-X2(SEQ ID NO: 985), G-F-K-G-l-G-X2(SEQ ID NO: 992), G-F-K-G-Y-V-X2(SEQ ID NO: 986), G-F-K-G-l-V-X2(SEQ ID NO: 993),

[0849] G-F-L-G-l-A6-X2(SEQ ID NO: 272), G-F-L-G-Y-A6-X2(SEQ ID NO: 273), G-F-L-G-A5-S-X2(SEQ ID NO: 274), G-F-L-G-A5-T-X2(SEQ ID NO: 275),

[0850] GAR-P04562WO16 Application (final) docx G-F-L-G-A5-C-X2(SEQ ID NO: 994), G-F-L-G-A5-N-X2(SEQ ID NO: 995), G-F-L-G-A5-Q-X2(SEQ ID NO: 996), G-F-L-G-A5-Y-X2(SEQ ID NO: 997), G-F-L-G-A5-A-X2(SEQ ID NO: 998), G-F-L-G-A5-G-X2(SEQ ID NO: 999), G-F-L-G-A5-V-X2(SEQ ID NO: 1000),

[0851] G-F-L-A4-l-S-X2(SEQ ID NO: 276), G-F-L-A4-l-T-X2(SEQ ID NO: 277), G-F-L-A4-l-C-X2(SEQ ID NO: 1001 ), G-F-L-A4-l-N-X2(SEQ ID NO: 1002), G-F-L-A4-l-Q-X2(SEQ ID NO: 1003), G-F-L-A4-l-Y-X2(SEQ ID NO: 1004), G-F-L-A4-l-A-X2(SEQ ID NO: 1005), G-F-L-A4-l-G-X2(SEQ ID NO: 1006), G-F-L-A4-l-V-X2(SEQ ID NO: 1007),

[0852] G-F-L-A4-Y-S-X2(SEQ ID NO: 278), G-F-L-A4-Y-T-X2(SEQ ID NO: 279), G-F-L-A4-Y-C-X2(SEQ ID NO: 1008), G-F-L-A4-Y-N-X2(SEQ ID NO: 1009), G-F-L-A4-Y-Q-X2(SEQ ID NO: 1010), G-F-L-A4-Y-Y-X2(SEQ ID NO: 1011 ), G-F-L-A4-Y-A-X2(SEQ ID NO: 1012), G-F-L-A4-Y-G-X2(SEQ ID NO: 1013), G-F-L-A4-Y-V-X2(SEQ ID NO: 1014),

[0853] G-F-L-G-Y-S-X2(SEQ ID NO: 280), G-F-L-G-l-S-X2(SEQ ID NO: 281 ), G-F-L-G-Y-T-X2(SEQ ID NO: 282), G-F-L-G-l-T-X2(SEQ ID NO: 283), G-F-L-G-Y-C-X2(SEQ ID NO: 1015), G-F-L-G-l-C-X2(SEQ ID NO: 1022), G-F-L-G-Y-N-X2(SEQ ID NO: 1016), G-F-L-G-l-N-X2(SEQ ID NO: 1023), G-F-L-G-Y-Q-X2(SEQ ID NO: 1017), G-F-L-G-l-Q-X2(SEQ ID NO: 1024),

[0854] GAR-P04562WO16 Application (final) docx G-F-L-G-Y-Y-X2(SEQ ID NO: 1018), G-F-L-G-l-Y-X2(SEQ ID NO: 1025), G-F-L-G-Y-A-X2(SEQ ID NO: 1019), G-F-L-G-l-A-X2(SEQ ID NO: 1026), G-F-L-G-Y-G-X2(SEQ ID NO: 1020), G-F-L-G-l-G-X2(SEQ ID NO: 1027), G-F-L-G-Y-V-X2(SEQ ID NO: 1021 ), G-F-L-G-l-V-X2(SEQ ID NO: 1028),

[0855] X4-R-G-l-A6-L-X3(SEQ ID NO: 284), X4-R-G-Y-A6-L-X3(SEQ ID NO: 285), X4-R-G-A5-S-L-X3(SEQ ID NO: 286), X4-R-G-A5-T-L-X3(SEQ ID NO: 287), X4-R-G-A5-C-L-X3(SEQ ID NO: 1029), X4-R-G-A5-N-L-X3(SEQ ID NO: 1030), X4-R-G-A5-Q-L-X3(SEQ ID NO: 1031 ), X4-R-G-A5-Y-L-X3(SEQ ID NO: 1032), X4-R-G-A5-A-L-X3(SEQ ID NO: 1033), X4-R-G-A5-G-L-X3(SEQ ID NO: 1034), X4-R-G-A5-V-L-X3(SEQ ID NO: 1035),

[0856] X4-R-A4-l-S-L-X3(SEQ ID NO: 288), X4-R-A4-l-T-L-X3(SEQ ID NO: 289), X4-R-A4-l-C-L-X3(SEQ ID NO: 1036), X4-R-A4-l-N-L-X3(SEQ ID NO: 1037), X4-R-A4-l-Q-L-X3(SEQ ID NO: 1038), X4-R-A4-l-Y-L-X3(SEQ ID NO: 1039), X4-R-A4-l-A-L-X3(SEQ ID NO: 1040), X4-R-A4-l-G-L-X3(SEQ ID NO: 1041 ), X4-R-A4-l-V-L-X3(SEQ ID NO: 1042),

[0857] X4-R-A4-Y-S-L-X3(SEQ ID NO: 290), X4-R-A4-Y-T-L-X3(SEQ ID NO: 291 ), X4-R-A4-Y-C-L-X3(SEQ ID NO: 1043), X4-R-A4-Y-N-L-X3(SEQ ID NO: 1044), X4-R-A4-Y-Q-L-X3(SEQ ID NO: 1045), X4-R-A4-Y-Y-L-X3(SEQ ID NO: 1046), X4-R-A4-Y-A-L-X3(SEQ ID NO: 1047),

[0858] GAR-P04562WO16 Application (final) docx X4-R-A4-Y-G-L-X3(SEQ ID NO: 1048), X4-R-A4-Y-V-L-X3(SEQ ID NO: 1049),

[0859] X4-R-G-Y-S-L-X3(SEQ ID NO: 292), X4-R-G-l-S-L-X3(SEQ ID NO: 293), X4-R-G-Y-T-L-X3(SEQ ID NO: 294), X4-R-G-l-T-L-X3(SEQ ID NO: 295), X4-R-G-Y-C-L-X3(SEQ ID NO: 1050), X4-R-G-l-C-L-X3(SEQ ID NO: 1057), X4-R-G-Y-N-L-X3(SEQ ID NO: 1051 ), X4-R-G-l-N-L-X3(SEQ ID NO: 1058), X4-R-G-Y-Q-L-X3(SEQ ID NO: 1052), X4-R-G-l-Q-L-X3(SEQ ID NO: 1059), X4-R-G-Y-Y-L-X3(SEQ ID NO: 1053), X4-R-G-l-Y-L-X3(SEQ ID NO: 1060), X4-R-G-Y-A-L-X3(SEQ ID NO: 1054), X4-R-G-l-A-L-X3(SEQ ID NO: 1061 ), X4-R-G-Y-G-L-X3(SEQ ID NO: 1055), X4-R-G-l-G-L-X3(SEQ ID NO: 1062), X4-R-G-Y-V-L-X3(SEQ ID NO: 1056), X4-R-G-l-V-L-X3(SEQ ID NO: 1063),

[0860] X4-K-G-l-A6-L-X3(SEQ ID NO: 296), X4-K-G-Y-A6-L-X3(SEQ ID NO: 297), X4-K-G-A5-S-L-X3(SEQ ID NO: 298), X4-K-G-A5-T-L-X3(SEQ ID NO: 299), X4-K-G-A5-C-L-X3(SEQ ID NO: 1064), X4-K-G-A5-N-L-X3(SEQ ID NO: 1065), X4-K-G-A5-Q-L-X3(SEQ ID NO: 1066), X4-K-G-A5-Y-L-X3(SEQ ID NO: 1067), X4-K-G-A5-A-L-X3(SEQ ID NO: 1068), X4-K-G-A5-G-L-X3(SEQ ID NO: 1069), X4-K-G-A5-V-L-X3(SEQ ID NO: 1070),

[0861] X4-K-A4-l-S-L-X3(SEQ ID NO: 300), X4-K-A4-l-T-L-X3(SEQ ID NO: 301 ), X4-K-A4-l-C-L-X3(SEQ ID NO: 1071 ), X4-K-A4-l-N-L-X3(SEQ ID NO: 1072),

[0862] GAR-P04562WO16 Application (final) docx X4-K-A4-l-Q-L-X3(SEQ ID NO: 1073), X4-K-A4-l-Y-L-X3(SEQ ID NO: 1074), X4-K-A4-l-A-L-X3(SEQ ID NO: 1075), X4-K-A4-l-G-L-X3(SEQ ID NO: 1076), X4-K-A4-l-V-L-X3(SEQ ID NO: 1077),

[0863] X4-K-A4-Y-S-L-X3(SEQ ID NO: 302), X4-K-A4-Y-T-L-X3(SEQ ID NO: 303), X4-K-A4-Y-C-L-X3(SEQ ID NO: 1078), X4-K-A4-Y-N-L-X3(SEQ ID NO: 1079), X4-K-A4-Y-Q-L-X3(SEQ ID NO: 1080), X4-K-A4-Y-Y-L-X3(SEQ ID NO: 1081 ), X4-K-A4-Y-A-L-X3(SEQ ID NO: 1082), X4-K-A4-Y-G-L-X3(SEQ ID NO: 1083), X4-K-A4-Y-V-L-X3(SEQ ID NO: 1084),

[0864] X4-K-G-Y-S-L-X3(SEQ ID NO: 304), X4-K-G-l-S-L-X3(SEQ ID NO: 305), X4-K-G-Y-T-L-X3(SEQ ID NO: 306), X4-K-G-l-T-L-X3(SEQ ID NO: 307), X4-K-G-Y-C-L-X3(SEQ ID NO: 1085), X4-K-G-l-C-L-X3(SEQ ID NO: 1092), X4-K-G-Y-N-L-X3(SEQ ID NO: 1086), X4-K-G-l-N-L-X3(SEQ ID NO: 1093), X4-K-G-Y-Q-L-X3(SEQ ID NO: 1087), X4-K-G-l-Q-L-X3(SEQ ID NO: 1094), X4-K-G-Y-Y-L-X3(SEQ ID NO: 1088), X4-K-G-l-Y-L-X3(SEQ ID NO: 1095), X4-K-G-Y-A-L-X3(SEQ ID NO: 1089), X4-K-G-l-A-L-X3(SEQ ID NO: 1096), X4-K-G-Y-G-L-X3(SEQ ID NO: 1090), X4-K-G-l-G-L-X3(SEQ ID NO: 1097), X4-K-G-Y-V-L-X3(SEQ ID NO: 1091 ), X4-K-G-l-V-L-X3(SEQ ID NO: 1098),

[0865] X4-L-G-l-A6-L-X3(SEQ ID NO: 308), X4-L-G-Y-A6-L-X3(SEQ ID NO: 309), X4-L-G-A5-S-L-X3(SEQ ID NO: 101 ),

[0866] GAR-P04562WO16 Application (final) docx -ABK

[0867] 73

[0868] X4-L-G-A5-T-L-X3(SEQ ID NO: 102), X4-L-G-A5-C-L-X3(SEQ ID NO: 1099), X4-L-G-A5-N-L-X3(SEQ ID NO: 1100), X4-L-G-A5-Q-L-X3(SEQ ID NO: 1101 ), X4-L-G-A5-Y-L-X3(SEQ ID NO: 1102), X4-L-G-A5-A-L-X3(SEQ ID NO: 1103), X4-L-G-A5-G-L-X3(SEQ ID NO: 1104), X4-L-G-A5-V-L-X3(SEQ ID NO: 1105),

[0869] X4-L-A4-l-S-L-X3(SEQ ID NO: 103), X4-L-A4-l-T-L-X3(SEQ ID NO: 104), X4-L-A4-l-C-L-X3(SEQ ID NO: 1106), X4-L-A4-l-N-L-X3(SEQ ID NO: 1107), X4-L-A4-l-Q-L-X3(SEQ ID NO: 1108), X4-L-A4-l-Y-L-X3(SEQ ID NO: 1109), X4-L-A4-l-A-L-X3(SEQ ID NO: 1110), X4-L-A4-l-G-L-X3(SEQ ID NO: 1111 ), X4-L-A4-l-V-L-X3(SEQ ID NO: 1112),

[0870] X4-L-A4-Y-S-L-X3(SEQ ID NO: 105), X4-L-A4-Y-T-L-X3(SEQ ID NO: 106), X4-L-A4-Y-C-L-X3(SEQ ID NO: 1113), X4-L-A4-Y-N-L-X3(SEQ ID NO: 1114), X4-L-A4-Y-Q-L-X3(SEQ ID NO: 1115), X4-L-A4-Y-Y-L-X3(SEQ ID NO: 1116), X4-L-A4-Y-A-L-X3(SEQ ID NO: 1117), X4-L-A4-Y-G-L-X3(SEQ ID NO: 1118), X4-L-A4-Y-V-L-X3(SEQ ID NO: 1119),

[0871] X4-L-G-Y-S-L-X3(SEQ ID NO: 107), X4-L-G-l-S-L-X3(SEQ ID NO: 108), X4-L-G-Y-T-L-X3(SEQ ID NO: 109), X4-L-G-l-T-L-X3(SEQ ID NO: 110), X4-L-G-Y-C-L-X3(SEQ ID NO: 1120), X4-L-G-l-C-L-X3(SEQ ID NO: 1127), X4-L-G-Y-N-L-X3(SEQ ID NO: 1121 ), X4-L-G-l-N-L-X3(SEQ ID NO: 1128), X4-L-G-Y-Q-L-X3(SEQ ID NO: 1122),

[0872] GAR-P04562WO16 Application (final) docx -ABK;

[0873] 74

[0874] X4-L-G-l-Q-L-X3(SEQ ID NO: 1129), X4-L-G-Y-Y-L-X3(SEQ ID NO: 1123), X4-L-G-l-Y-L-X3(SEQ ID NO: 1130), X4-L-G-Y-A-L-X3(SEQ ID NO: 1124), X4-L-G-l-A-L-X3(SEQ ID NO: 1131 ), X4-L-G-Y-G-L-X3(SEQ ID NO: 1125), X4-L-G-l-G-L-X3(SEQ ID NO: 1132), X4-L-G-Y-V-L-X3(SEQ ID NO: 1126), X4-L-G-l-V-L-X3(SEQ ID NO: 1133), wherein

[0875] X1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or C-A1-A2-A3-; wherein C represents the amino acid cysteine; preferably X11 represents -H, A1-A2-A3-, A2-A3- or A3-; X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9- A10-A11;

[0876] X3represents -H, -A8, -A8-A9, -A8-A9-A10, or -A8-A9-A10-A11; X4represents -H, A1-A2-, or A2-; X5represents -H, -A9, -A9-A10, or -A9-A10-A11; X6represents -H, or A1-; X7represents -H, -A10, or -A10-A11; X8represents -H, or -A11. wherein

[0877] A1represents an amino acid selected from G and A;

[0878] A2represents an amino acid selected from Y, F, and W;

[0879] A3represents an amino acid selected from R, K and L;

[0880] A4represents an amino acid selected from G, and A;

[0881] A5represents an amino acid selected from I, Y, Q, N, L, and F;

[0882] A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;

[0883] A7represents an amino acid selected from L, I, and V;

[0884] A8represents an amino acid selected from A, G, and V;

[0885] A9represents an amino acid selected from K, N, and Q;

[0886] A10represents an amino acid selected from W, and F;

[0887] A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G; and more preferably wherein

[0888] A1represents an amino acid selected from G and A;

[0889] A2represents an amino acid selected from Y, and F;

[0890] A3represents an amino acid selected from R, K and L;

[0891] GAR-P04562WO16 Application (final) docx A4represents an amino acid selected from G, and A;

[0892] A5represents an amino acid selected from I, and Y;

[0893] A6represents an amino acid selected from S, T, C, N, and Y;

[0894] A7represents an amino acid selected from L, and I;

[0895] A8represents an amino acid selected from A, and G;

[0896] A9represents an amino acid selected from K and N;

[0897] A10represents an amino acid selected from W, and F;

[0898] A11represents an amino acid selected from M, M-NH2, L, I, and V; and still more preferably wherein

[0899] A1represents G;

[0900] A2represents an amino acid selected from Y, and F;

[0901] A3represents an amino acid selected from R, K and L;

[0902] A4represents G;

[0903] A5represents an amino acid selected from I, and Y;

[0904] A6represents an amino acid selected from S and T;

[0905] A7represents L;

[0906] A8represents A;

[0907] A9represents an amino acid selected from K and N;

[0908] A10represents W;

[0909] A11represents an amino acid selected from M, M-NH2, and V.

[0910] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313), GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANVW (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14), YRGINLANWM (SEQ ID NO: 1134), YRGINLANW (SEQ ID NO: 1135), GFRGINLANWM (SEQ ID NO: 1136), GFRGINLANWV (SEQ ID NO: 1137), GFRGINLANWM-NH2 (SEQ ID NO: 1138), GYKGINLANWM (SEQ ID NO: 1139), GYKGINLANWV (SEQ ID NO: 1140), GYKGINLANWM-NH2 (SEQ ID NO: 1141 ), GYRGYNLANWM (SEQ ID NO: 1142), GYRGYNLANWV (SEQ ID NO: 1143), GYRGYNLANWM-NH2 (SEQ ID NO: 1144),

[0911] GAR-P04562WO16 Application (final) docx GYRGINLAKWM (SEQ ID NO: 1145), GYRGINLAKWV (SEQ ID NO: 1146), GYRGINLAKWM-NH2 (SEQ ID NO: 1147), GYRGINLANWM (SEQ ID NO: 1148), GYRGINLANWV (SEQ ID NO: 1149), GYLGINLANW (SEQ ID NO: 1150), GYRGINLANWM-NH2 (SEQ ID NO: 1151 ), YRGICLANWM (SEQ ID NO: 1152), YRGICLANW (SEQ ID NO: 1153), GFRGICLANWM (SEQ ID NO: 1154), GFRGICLANWV (SEQ ID NO: 1155), GFRGICLANWM-NH2 (SEQ ID NO: 1156), GYKGICLANWM (SEQ ID NO: 1157), GYKGICLANWV (SEQ ID NO: 1158), GYKGICLANWM-NH2 (SEQ ID NO: 1159), GYRGYCLANWM (SEQ ID NO: 1160), GYRGYCLANWV (SEQ ID NO: 1161 ), GYRGYCLANWM-NH2 (SEQ ID NO: 1162), GYRGICLAKWM (SEQ ID NO: 1163), GYRGICLAKWV (SEQ ID NO: 1164), GYRGICLAKWM-NH2 (SEQ ID NO: 1165), GYRGICLANWM (SEQ ID NO: 1166), GYRGICLANWV (SEQ ID NO: 1167), GYLGICLANW (SEQ ID NO: 1168), GYRGICLANWM-NH2 (SEQ ID NO: 1169), YRGIQLANWM (SEQ ID NO: 1170), YRGIQLANW (SEQ ID NO: 1171 ), GFRGIQLANWM (SEQ ID NO: 1172), GFRGIQLANWV (SEQ ID NO: 1173), GFRGIQLANWM-NH2 (SEQ ID NO: 1174), GYKGIQLANWM (SEQ ID NO: 1175), GYKGIQLANWV (SEQ ID NO: 1176), GYKGIQLANWM-NH2 (SEQ ID NO: 1177), GYRGYQLANWM (SEQ ID NO: 1178), GYRGYQLANWV (SEQ ID NO: 1179), GYRGYQLANWM-NH2 (SEQ ID NO: 1180), GYRGIQLAKWM (SEQ ID NO: 1181 ), GYRGIQLAKWV (SEQ ID NO: 1182), GYRGIQLAKWM-NH2 (SEQ ID NO: 1183), GYRGIQLANWM (SEQ ID NO: 1184), GYRGIQLANWV (SEQ ID NO: 1185), GYLGIQLANW (SEQ ID NO: 1186), GYRGIQLANWM-NH2 (SEQ ID NO: 1187), YRGIYLANWM (SEQ ID NO: 1188), YRGIYLANW (SEQ ID NO: 1189), GFRGIYLANWM (SEQ ID NO: 1190), GFRGIYLANWV (SEQ ID NO: 1191), GFRGIYLANWM-NH2 (SEQ ID NO: 1192), GYKGIYLANWM (SEQ ID NO: 1193), GYKGIYLANWV (SEQ ID NO: 1194), GYKGIYLANWM-NH2 (SEQ ID NO: 1195), GYRGYYLANWM (SEQ ID NO: 1196), GYRGYYLANWV (SEQ ID NO: 1197), GYRGYYLANWM-NH2 (SEQ ID NO: 1198), GYRGIYLAKWM (SEQ ID NO: 1199), GYRGIYLAKWV (SEQ ID NO: 1200), GYRGIYLAKWM-NH2 (SEQ ID NO: 1201 ), GYRGIYLANWM (SEQ ID NO: 1202), GYRGIYLANWV (SEQ ID NO: 1203), GYLGIYLANW (SEQ ID NO: 1204), GYRGIYLANWM-NH2 (SEQ ID NO: 1205), YRGIALANWM (SEQ ID NO: 1206), YRGIALANW (SEQ ID NO: 1207), GFRGIALANWM (SEQ ID NO: 1208), GFRGIALANWV (SEQ ID NO: 1209), GFRGIALANWM-NH2 (SEQ ID NO: 1210), GYKGIALANWM (SEQ ID NO: 1211 ), GYKGIALANWV (SEQ ID NO: 1212), GYKGIALANWM-NH2 (SEQ ID NO: 1213), GYRGYALANWM (SEQ ID NO: 1214), GYRGYALANWV (SEQ ID NO: 1215), GYRGYALANWM-NH2 (SEQ ID NO: 1216), GYRGIALAKWM (SEQ ID NO: 1217), GYRGIALAKWV (SEQ ID NO: 1218), GYRGIALAKWM-NH2 (SEQ ID NO: 1219), GYRGIALANWM (SEQ ID NO: 1220),

[0912] GAR-P04562WO16 Application (final) docx GYRGIALANWV (SEQ ID NO: 1221 ), GYLGIALANW (SEQ ID NO: 1222), GYRGIALANWM-NH2 (SEQ ID NO: 1223), YRGIGLANWM (SEQ ID NO: 1224), YRGIGLANW (SEQ ID NO: 1225), GFRGIGLANWM (SEQ ID NO: 1226), GFRGIGLANWV (SEQ ID NO: 1227), GFRGIGLANWM-NH2 (SEQ ID NO: 1228), GYKGIGLANWM (SEQ ID NO: 1229), GYKGIGLANWV (SEQ ID NO: 1230), GYKGIGLANWM-NH2 (SEQ ID NO: 1231 ), GYRGYGLANWM (SEQ ID NO: 1232), GYRGYGLANWV (SEQ ID NO: 1233), GYRGYGLANWM-NH2 (SEQ ID NO: 1234), GYRGIGLAKWM (SEQ ID NO: 1235), GYRGIGLAKWV (SEQ ID NO: 1236), GYRGIGLAKWM-NH2 (SEQ ID NO: 1237), GYRGIGLANWM (SEQ ID NO: 1238), GYRGIGLANWV (SEQ ID NO: 1239), GYLGIGLANW (SEQ ID NO: 1240), GYRGIGLANWM-NH2 (SEQ ID NO: 1241 ), YRGIVLANWM (SEQ ID NO: 1242), YRGIVLANW (SEQ ID NO: 1243), GFRGIVLANWM (SEQ ID NO: 1244), GFRGIVLANWV (SEQ ID NO: 1245), GFRGIVLANWM-NH2 (SEQ ID NO: 1246), GYKGIVLANWM (SEQ ID NO: 1247), GYKGIVLANWV (SEQ ID NO: 1248), GYKGIVLANWM-NH2 (SEQ ID NO: 1249), GYRGYVLANWM (SEQ ID NO: 1250), GYRGYVLANWV (SEQ ID NO: 1251 ), GYRGYVLANWM-NH2 (SEQ ID NO: 1252), GYRGIVLAKWM (SEQ ID NO: 1253), GYRGIVLAKWV (SEQ ID NO: 1254), GYRGIVLAKWM-NH2 (SEQ ID NO: 1255), GYRGIVLANWM (SEQ ID NO: 1256), GYRGIVLANWV (SEQ ID NO: 1257), GYLGIVLANW (SEQ ID NO: 1258), GYRGIVLANWM-NH2 (SEQ ID NO: 1259), CGYLGIS (SEQ ID NO: 1260), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261 ), CGYRGITLANWM (SEQ ID NO: 1262), CYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264),

[0913] CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266),

[0914] CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268),

[0915] CGYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270),

[0916] CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

[0917] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313), GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANVW (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321),

[0918] GAR-P04562WO16 Application (final) docx GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2(SEQ ID NO: 14), YRGINLANWM (SEQ ID NO: 1134), YRGINLANW (SEQ ID NO: 1135), GFRGINLANWM (SEQ ID NO: 1136), GFRGINLANWV (SEQ ID NO: 1137), GFRGINLANWM-NH2 (SEQ ID NO: 1138), GYKGINLANWM (SEQ ID NO: 1139), GYKGINLANWV (SEQ ID NO: 1140), GYKGINLANWM-NH2 (SEQ ID NO: 1141 ), GYRGYNLANWM (SEQ ID NO: 1142), GYRGYNLANWV (SEQ ID NO: 1143), GYRGYNLANWM-NH2 (SEQ ID NO: 1144), GYRGINLAKWM (SEQ ID NO: 1145), GYRGINLAKWV (SEQ ID NO: 1146), GYRGINLAKWM-NH2 (SEQ ID NO: 1147), GYRGINLANWM (SEQ ID NO: 1148), GYRGINLANWV (SEQ ID NO: 1149), GYLGINLANW (SEQ ID NO: 1150), GYRGINLANWM-NH2 (SEQ ID NO: 1151 ), YRGICLANWM (SEQ ID NO: 1152), YRGICLANW (SEQ ID NO: 1153), GFRGICLANWM (SEQ ID NO: 1154), GFRGICLANWV (SEQ ID NO: 1155), GFRGICLANWM-NH2 (SEQ ID NO: 1156), GYKGICLANWM (SEQ ID NO: 1157), GYKGICLANWV (SEQ ID NO: 1158), GYKGICLANWM-NH2 (SEQ ID NO: 1159), GYRGYCLANWM (SEQ ID NO: 1160), GYRGYCLANWV (SEQ ID NO: 1161 ), GYRGYCLANWM-NH2 (SEQ ID NO: 1162), GYRGICLAKWM (SEQ ID NO: 1163), GYRGICLAKWV (SEQ ID NO: 1164), GYRGICLAKWM-NH2 (SEQ ID NO: 1165), GYRGICLANWM (SEQ ID NO: 1166), GYRGICLANWV (SEQ ID NO: 1167), GYLGICLANW (SEQ ID NO: 1168), GYRGICLANWM-NH2 (SEQ ID NO: 1169), YRGIQLANWM (SEQ ID NO: 1170), YRGIQLANW (SEQ ID NO: 1171 ), GFRGIQLANWM (SEQ ID NO: 1172), GFRGIQLANWV (SEQ ID NO: 1173), GFRGIQLANWM-NH2 (SEQ ID NO: 1174), GYKGIQLANWM (SEQ ID NO: 1175), GYKGIQLANWV (SEQ ID NO: 1176), GYKGIQLANWM-NH2 (SEQ ID NO: 1177), GYRGYQLANWM (SEQ ID NO: 1178), GYRGYQLANWV (SEQ ID NO: 1179), GYRGYQLANWM-NH2 (SEQ ID NO: 1180), GYRGIQLAKWM (SEQ ID NO: 1181 ), GYRGIQLAKWV (SEQ ID NO: 1182), GYRGIQLAKWM-NH2 (SEQ ID NO: 1183), GYRGIQLANWM (SEQ ID NO: 1184), GYRGIQLANWV (SEQ ID NO: 1185), GYLGIQLANW (SEQ ID NO: 1186), GYRGIQLANWM-NH2 (SEQ ID NO: 1187), YRGIYLANWM (SEQ ID NO: 1188), YRGIYLANW (SEQ ID NO: 1189), GFRGIYLANWM (SEQ ID NO: 1190), GFRGIYLANWV (SEQ ID NO: 1191 ), GFRGIYLANWM-NH2 (SEQ ID NO: 1192), GYKGIYLANWM (SEQ ID NO: 1193), GYKGIYLANWV (SEQ ID NO: 1194), GYKGIYLANWM-NH2 (SEQ ID NO: 1195), GYRGYYLANWM (SEQ ID NO: 1196), GYRGYYLANWV (SEQ ID NO: 1197), GYRGYYLANWM-NH2 (SEQ ID NO: 1198), GYRGIYLAKWM (SEQ ID NO: 1199), GYRGIYLAKWV (SEQ ID NO: 1200), GYRGIYLAKWM-NH2 (SEQ ID NO: 1201 ), GYRGIYLANWM (SEQ ID NO: 1202), GYRGIYLANWV (SEQ ID NO: 1203), GYLGIYLANW (SEQ ID NO: 1204), GYRGIYLANWM-NH2 (SEQ ID NO: 1205), YRGIALANWM (SEQ ID NO: 1206),

[0919] GAR-P04562WO16 Application (final) docx YRGIALANW (SEQ ID NO: 1207), GFRGIALANWM (SEQ ID NO: 1208), GFRGIALANWV (SEQ ID NO: 1209), GFRGIALANWM-NH2(SEQ ID NO: 1210), GYKGIALANWM (SEQ ID NO: 1211 ), GYKGIALANWV (SEQ ID NO: 1212), GYKGIALANWM-NH2 (SEQ ID NO: 1213), GYRGYALANWM (SEQ ID NO: 1214), GYRGYALANWV (SEQ ID NO: 1215), GYRGYALANWM-NH2 (SEQ ID NO: 1216), GYRGIALAKWM (SEQ ID NO: 1217), GYRGIALAKWV (SEQ ID NO: 1218), GYRGIALAKWM-NH2 (SEQ ID NO: 1219), GYRGIALANWM (SEQ ID NO: 1220), GYRGIALANWV (SEQ ID NO: 1221 ), GYLGIALANW (SEQ ID NO: 1222), GYRGIALANWM-NH2 (SEQ ID NO: 1223), YRGIGLANWM (SEQ ID NO: 1224), YRGIGLANW (SEQ ID NO: 1225), GFRGIGLANWM (SEQ ID NO: 1226), GFRGIGLANWV (SEQ ID NO: 1227), GFRGIGLANWM-NH2 (SEQ ID NO: 1228), GYKGIGLANWM (SEQ ID NO: 1229), GYKGIGLANWV (SEQ ID NO: 1230), GYKGIGLANWM-NH2 (SEQ ID NO: 1231 ), GYRGYGLANWM (SEQ ID NO: 1232), GYRGYGLANWV (SEQ ID NO: 1233), GYRGYGLANWM-NH2 (SEQ ID NO: 1234), GYRGIGLAKWM (SEQ ID NO: 1235), GYRGIGLAKWV (SEQ ID NO: 1236), GYRGIGLAKWM-NH2 (SEQ ID NO: 1237), GYRGIGLANWM (SEQ ID NO: 1238), GYRGIGLANWV (SEQ ID NO: 1239), GYLGIGLANW (SEQ ID NO: 1240), GYRGIGLANWM-NH2 (SEQ ID NO: 1241 ), YRGIVLANWM (SEQ ID NO: 1242), YRGIVLANW (SEQ ID NO: 1243), GFRGIVLANWM (SEQ ID NO: 1244), GFRGIVLANWV (SEQ ID NO: 1245), GFRGIVLANWM-NH2 (SEQ ID NO: 1246), GYKGIVLANWM (SEQ ID NO: 1247), GYKGIVLANWV (SEQ ID NO: 1248), GYKGIVLANWM-NH2 (SEQ ID NO: 1249), GYRGYVLANWM (SEQ ID NO: 1250), GYRGYVLANWV (SEQ ID NO: 1251 ), GYRGYVLANWM-NH2 (SEQ ID NO: 1252), GYRGIVLAKWM (SEQ ID NO: 1253), GYRGIVLAKWV (SEQ ID NO: 1254), GYRGIVLAKWM-NH2 (SEQ ID NO: 1255), GYRGIVLANWM (SEQ ID NO: 1256), GYRGIVLANWV (SEQ ID NO: 1257), GYLGIVLANW (SEQ ID NO: 1258), GYRGIVLANWM-NH2 (SEQ ID NO: 1259), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261 ), CGYRGITLANWM (SEQ ID NO: 1262), CYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264), CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266), CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268), CGYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270), CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

[0920] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313),

[0921] GAR-P04562WO16 Application (final) docx GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANVW (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321 ), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14), YRGINLANWM (SEQ ID NO: 1134), YRGINLANW (SEQ ID NO: 1135), GFRGINLANWM (SEQ ID NO: 1136), GFRGINLANWV (SEQ ID NO: 1137), GFRGINLANWM-NH2 (SEQ ID NO: 1138), GYKGINLANWM (SEQ ID NO: 1139), GYKGINLANWV (SEQ ID NO: 1140), GYKGINLANWM-NH2 (SEQ ID NO: 1141 ), GYRGYNLANWM (SEQ ID NO: 1142), GYRGYNLANWV (SEQ ID NO: 1143), GYRGYNLANWM-NH2 (SEQ ID NO: 1144), GYRGINLAKWM (SEQ ID NO: 1145), GYRGINLAKWV (SEQ ID NO: 1146), GYRGINLAKWM-NH2 (SEQ ID NO: 1147), GYRGINLANWM (SEQ ID NO: 1148), GYRGINLANWV (SEQ ID NO: 1149), GYLGINLANW (SEQ ID NO: 1150), GYRGINLANWM-NH2 (SEQ ID NO: 1151 ), YRGICLANWM (SEQ ID NO: 1152), YRGICLANW (SEQ ID NO: 1153), GFRGICLANWM (SEQ ID NO: 1154), GFRGICLANWV (SEQ ID NO: 1155), GFRGICLANWM-NH2 (SEQ ID NO: 1156), GYKGICLANWM (SEQ ID NO: 1157), GYKGICLANWV (SEQ ID NO: 1158), GYKGICLANWM-NH2 (SEQ ID NO: 1159), GYRGYCLANWM (SEQ ID NO: 1160), GYRGYCLANWV (SEQ ID NO: 1161 ), GYRGYCLANWM-NH2 (SEQ ID NO: 1162), GYRGICLAKWM (SEQ ID NO: 1163), GYRGICLAKWV (SEQ ID NO: 1164), GYRGICLAKWM-NH2 (SEQ ID NO: 1165), GYRGICLANWM (SEQ ID NO: 1166), GYRGICLANWV (SEQ ID NO: 1167), GYLGICLANW (SEQ ID NO: 1168), GYRGICLANWM-NH2 (SEQ ID NO: 1169), YRGIQLANWM (SEQ ID NO: 1170), YRGIQLANW (SEQ ID NO: 1171 ), GFRGIQLANWM (SEQ ID NO: 1172), GFRGIQLANWV (SEQ ID NO: 1173), GFRGIQLANWM-NH2 (SEQ ID NO: 1174), GYKGIQLANWM (SEQ ID NO: 1175), GYKGIQLANWV (SEQ ID NO: 1176), GYKGIQLANWM-NH2 (SEQ ID NO: 1177), GYRGYQLANWM (SEQ ID NO: 1178), GYRGYQLANWV (SEQ ID NO: 1179), GYRGYQLANWM-NH2 (SEQ ID NO: 1180), GYRGIQLAKWM (SEQ ID NO: 1181 ), GYRGIQLAKWV (SEQ ID NO: 1182), GYRGIQLAKWM-NH2 (SEQ ID NO: 1183), GYRGIQLANWM (SEQ ID NO: 1184), GYRGIQLANWV (SEQ ID NO: 1185), GYLGIQLANW (SEQ ID NO: 1186), GYRGIQLANWM-NH2 (SEQ ID NO: 1187), YRGIYLANWM (SEQ ID NO: 1188), YRGIYLANW (SEQ ID NO: 1189), GFRGIYLANWM (SEQ ID NO: 1190), GFRGIYLANWV (SEQ ID NO: 1191 ), GFRGIYLANWM-NH2 (SEQ ID NO: 1192), GYKGIYLANWM (SEQ ID NO: 1193), GYKGIYLANWV (SEQ ID NO: 1194),

[0922] GAR-P04562WO16 Application (final) docx GYKGIYLANWM-NH2 (SEQ ID NO: 1195), GYRGYYLANWM (SEQ ID NO: 1196), GYRGYYLANWV (SEQ ID NO: 1197), GYRGYYLANWM-NH2(SEQ ID NO: 1198), GYRGIYLAKWM (SEQ ID NO: 1199), GYRGIYLAKWV (SEQ ID NO: 1200), GYRGIYLAKWM-NH2 (SEQ ID NO: 1201 ), GYRGIYLANWM (SEQ ID NO: 1202), GYRGIYLANWV (SEQ ID NO: 1203), GYLGIYLANW (SEQ ID NO: 1204), GYRGIYLANWM-NH2 (SEQ ID NO: 1205), YRGIALANWM (SEQ ID NO: 1206), YRGIALANW (SEQ ID NO: 1207), GFRGIALANWM (SEQ ID NO: 1208), GFRGIALANWV (SEQ ID NO: 1209), GFRGIALANWM-NH2 (SEQ ID NO: 1210), GYKGIALANWM (SEQ ID NO: 1211 ), GYKGIALANWV (SEQ ID NO: 1212), GYKGIALANWM-NH2 (SEQ ID NO: 1213), GYRGYALANWM (SEQ ID NO: 1214), GYRGYALANWV (SEQ ID NO: 1215), GYRGYALANWM-NH2 (SEQ ID NO: 1216), GYRGIALAKWM (SEQ ID NO: 1217), GYRGIALAKWV (SEQ ID NO: 1218), GYRGIALAKWM-NH2 (SEQ ID NO: 1219), GYRGIALANWM (SEQ ID NO: 1220), GYRGIALANWV (SEQ ID NO: 1221 ), GYLGIALANW (SEQ ID NO: 1222), GYRGIALANWM-NH2 (SEQ ID NO: 1223), YRGIGLANWM (SEQ ID NO: 1224), YRGIGLANW (SEQ ID NO: 1225), GFRGIGLANWM (SEQ ID NO: 1226), GFRGIGLANWV (SEQ ID NO: 1227), GFRGIGLANWM-NH2 (SEQ ID NO: 1228), GYKGIGLANWM (SEQ ID NO: 1229), GYKGIGLANWV (SEQ ID NO: 1230), GYKGIGLANWM-NH2 (SEQ ID NO: 1231 ), GYRGYGLANWM (SEQ ID NO: 1232), GYRGYGLANWV (SEQ ID NO: 1233), GYRGYGLANWM-NH2 (SEQ ID NO: 1234), GYRGIGLAKWM (SEQ ID NO: 1235), GYRGIGLAKWV (SEQ ID NO: 1236), GYRGIGLAKWM-NH2 (SEQ ID NO: 1237), GYRGIGLANWM (SEQ ID NO: 1238), GYRGIGLANWV (SEQ ID NO: 1239), GYLGIGLANW (SEQ ID NO: 1240), GYRGIGLANWM-NH2 (SEQ ID NO: 1241 ), YRGIVLANWM (SEQ ID NO: 1242), YRGIVLANW (SEQ ID NO: 1243), GFRGIVLANWM (SEQ ID NO: 1244), GFRGIVLANWV (SEQ ID NO: 1245), GFRGIVLANWM-NH2 (SEQ ID NO: 1246), GYKGIVLANWM (SEQ ID NO: 1247), GYKGIVLANWV (SEQ ID NO: 1248), GYKGIVLANWM-NH2 (SEQ ID NO: 1249), GYRGYVLANWM (SEQ ID NO: 1250), GYRGYVLANWV (SEQ ID NO: 1251 ), GYRGYVLANWM-NH2 (SEQ ID NO: 1252), GYRGIVLAKWM (SEQ ID NO: 1253), GYRGIVLAKWV (SEQ ID NO: 1254), GYRGIVLAKWM-NH2 (SEQ ID NO: 1255), GYRGIVLANWM (SEQ ID NO: 1256), GYRGIVLANWV (SEQ ID NO: 1257), GYLGIVLANW (SEQ ID NO: 1258), and GYRGIVLANWM-NH2 (SEQ ID NO: 1259).

[0923] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313),

[0924] GAR-P04562WO16 Application (final) docx GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANVW (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321 ), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14), YRGINLANWM (SEQ ID NO: 1134), YRGINLANW (SEQ ID NO: 1135), GFRGINLANWM (SEQ ID NO: 1136), GFRGINLANWV (SEQ ID NO: 1137), GFRGINLANWM-NH2 (SEQ ID NO: 1138), GYKGINLANWM (SEQ ID NO: 1139), GYKGINLANWV (SEQ ID NO: 1140), GYKGINLANWM-NH2 (SEQ ID NO: 1141 ), GYRGYNLANWM (SEQ ID NO: 1142), GYRGYNLANWV (SEQ ID NO: 1143), GYRGYNLANWM-NH2 (SEQ ID NO: 1144), GYRGINLAKWM (SEQ ID NO: 1145), GYRGINLAKWV (SEQ ID NO: 1146), GYRGINLAKWM-NH2 (SEQ ID NO: 1147), GYRGINLANWM (SEQ ID NO: 1148), GYRGINLANWV (SEQ ID NO: 1149), GYLGINLANW (SEQ ID NO: 1150), GYRGINLANWM-NH2 (SEQ ID NO: 1151 ), YRGICLANWM (SEQ ID NO: 1152), YRGICLANW (SEQ ID NO: 1153), GFRGICLANWM (SEQ ID NO: 1154), GFRGICLANWV (SEQ ID NO: 1155), GFRGICLANWM-NH2 (SEQ ID NO: 1156), GYKGICLANWM (SEQ ID NO: 1157), GYKGICLANWV (SEQ ID NO: 1158), GYKGICLANWM-NH2 (SEQ ID NO: 1159), GYRGYCLANWM (SEQ ID NO: 1160), GYRGYCLANWV (SEQ ID NO: 1161 ), GYRGYCLANWM-NH2 (SEQ ID NO: 1162), GYRGICLAKWM (SEQ ID NO: 1163), GYRGICLAKWV (SEQ ID NO: 1164), GYRGICLAKWM-NH2 (SEQ ID NO: 1165), GYRGICLANWM (SEQ ID NO: 1166), GYRGICLANWV (SEQ ID NO: 1167), GYLGICLANW (SEQ ID NO: 1168), GYRGICLANWM-NH2 (SEQ ID NO: 1169), YRGIQLANWM (SEQ ID NO: 1170), YRGIQLANW (SEQ ID NO: 1171 ), GFRGIQLANWM (SEQ ID NO: 1172), GFRGIQLANWV (SEQ ID NO: 1173), GFRGIQLANWM-NH2 (SEQ ID NO: 1174), GYKGIQLANWM (SEQ ID NO: 1175), GYKGIQLANWV (SEQ ID NO: 1176), GYKGIQLANWM-NH2 (SEQ ID NO: 1177), GYRGYQLANWM (SEQ ID NO: 1178), GYRGYQLANWV (SEQ ID NO: 1179), GYRGYQLANWM-NH2 (SEQ ID NO: 1180), GYRGIQLAKWM (SEQ ID NO: 1181 ), GYRGIQLAKWV (SEQ ID NO: 1182), GYRGIQLAKWM-NH2 (SEQ ID NO: 1183), GYRGIQLANWM (SEQ ID NO: 1184), GYRGIQLANWV (SEQ ID NO: 1185), GYLGIQLANW (SEQ ID NO: 1186), GYRGIQLANWM-NH2 (SEQ ID NO: 1187), YRGIYLANWM (SEQ ID NO: 1188), YRGIYLANW (SEQ ID NO: 1189), GFRGIYLANWM (SEQ ID NO: 1190), GFRGIYLANWV (SEQ ID NO: 1191 ), GFRGIYLANWM-NH2 (SEQ ID NO: 1192), GYKGIYLANWM (SEQ ID NO: 1193), GYKGIYLANWV (SEQ ID NO: 1194),

[0925] GAR-P04562WO16 Application (final) docx GYKGIYLANWM-NH2 (SEQ ID NO: 1195), GYRGYYLANWM (SEQ ID NO: 1196), GYRGYYLANWV (SEQ ID NO: 1197), GYRGYYLANWM-NH2(SEQ ID NO: 1198), GYRGIYLAKWM (SEQ ID NO: 1199), GYRGIYLAKWV (SEQ ID NO: 1200), GYRGIYLAKWM-NH2 (SEQ ID NO: 1201 ), GYRGIYLANWM (SEQ ID NO: 1202), GYRGIYLANWV (SEQ ID NO: 1203), GYLGIYLANW (SEQ ID NO: 1204), GYRGIYLANWM-NH2 (SEQ ID NO: 1205), YRGIALANWM (SEQ ID NO: 1206), YRGIALANW (SEQ ID NO: 1207), GFRGIALANWM (SEQ ID NO: 1208), GFRGIALANWV (SEQ ID NO: 1209), GFRGIALANWM-NH2 (SEQ ID NO: 1210), GYKGIALANWM (SEQ ID NO: 1211 ), GYKGIALANWV (SEQ ID NO: 1212), GYKGIALANWM-NH2 (SEQ ID NO: 1213), GYRGYALANWM (SEQ ID NO: 1214), GYRGYALANWV (SEQ ID NO: 1215), GYRGYALANWM-NH2 (SEQ ID NO: 1216), GYRGIALAKWM (SEQ ID NO: 1217), GYRGIALAKWV (SEQ ID NO: 1218), GYRGIALAKWM-NH2 (SEQ ID NO: 1219), GYRGIALANWM (SEQ ID NO: 1220), GYRGIALANWV (SEQ ID NO: 1221 ), GYLGIALANW (SEQ ID NO: 1222), GYRGIALANWM-NH2 (SEQ ID NO: 1223), YRGIGLANWM (SEQ ID NO: 1224), YRGIGLANW (SEQ ID NO: 1225), GFRGIGLANWM (SEQ ID NO: 1226), GFRGIGLANWV (SEQ ID NO: 1227), GFRGIGLANWM-NH2 (SEQ ID NO: 1228), GYKGIGLANWM (SEQ ID NO: 1229), GYKGIGLANWV (SEQ ID NO: 1230), GYKGIGLANWM-NH2 (SEQ ID NO: 1231 ), GYRGYGLANWM (SEQ ID NO: 1232), GYRGYGLANWV (SEQ ID NO: 1233), GYRGYGLANWM-NH2 (SEQ ID NO: 1234), GYRGIGLAKWM (SEQ ID NO: 1235), GYRGIGLAKWV (SEQ ID NO: 1236), GYRGIGLAKWM-NH2 (SEQ ID NO: 1237), GYRGIGLANWM (SEQ ID NO: 1238), GYRGIGLANWV (SEQ ID NO: 1239), GYLGIGLANW (SEQ ID NO: 1240), GYRGIGLANWM-NH2 (SEQ ID NO: 1241 ), YRGIVLANWM (SEQ ID NO: 1242), YRGIVLANW (SEQ ID NO: 1243), GFRGIVLANWM (SEQ ID NO: 1244), GFRGIVLANWV (SEQ ID NO: 1245), GFRGIVLANWM-NH2 (SEQ ID NO: 1246), GYKGIVLANWM (SEQ ID NO: 1247), GYKGIVLANWV (SEQ ID NO: 1248), GYKGIVLANWM-NH2 (SEQ ID NO: 1249), GYRGYVLANWM (SEQ ID NO: 1250), GYRGYVLANWV (SEQ ID NO: 1251 ), GYRGYVLANWM-NH2 (SEQ ID NO: 1252), GYRGIVLAKWM (SEQ ID NO: 1253), GYRGIVLAKWV (SEQ ID NO: 1254), GYRGIVLAKWM-NH2 (SEQ ID NO: 1255), GYRGIVLANWM (SEQ ID NO: 1256), GYRGIVLANWV (SEQ ID NO: 1257), GYLGIVLANW (SEQ ID NO: 1258), and GYRGIVLANWM-NH2 (SEQ ID NO: 1259.

[0926] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313),

[0927] GAR-P04562WO16 Application (final) docx GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANWV (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261), CGYRGITLANWM (SEQ ID NO: 1262), CYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264),

[0928] CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266),

[0929] CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268),

[0930] CGYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270),

[0931] CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

[0932] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313), GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANWV (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321 ), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261 ), CGYRGITLANWM (SEQ ID NO: 1262), CYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264), CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266), CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268), CGYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270), CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

[0933] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6),

[0934] GAR-P04562WO16 Application (final) docx -=ABK

[0935] 85

[0936] GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2(SEQ ID NO: 313), GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANWV (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321 ), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14).

[0937] Preferred are peptides consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313), GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316), GYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANWV (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ), GYRGISLAKWV (SEQ ID NO: 320), GYRGISLAKWM-NH2 (SEQ ID NO: 321 ), GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), GYRGISLANWM-NH2 (SEQ ID NO: 14).

[0938] Very preferred are the following sequences: GYL-GIS (SEQ ID NO: 2),

[0939] GIS-LAN (SEQ ID NO: 3) YR-GIS-LANWM (SEQ ID NO: 4), YR-GIS-LANW (SEQ ID NO: 5), GFR-GIS-LANWM (SEQ ID NO: 6), GYK-GIS-LANWM (SEQ ID NO: 7), GYR-GIS-LANWM (SEQ ID NO: 8), GYR-GYS-LANWM (SEQ ID NO: 9), GYR-GIT-LANWM (SEQ ID NO: 10), GYR-GIS-LAKWM (SEQ ID NO: 11 ) GYR-GIS-LANWV (SEQ ID NO: 12), GYL-GIS-LANW (SEQ ID NO: 13), GYR-GIS-LANWM-NH2 (SEQ ID NO: 14) C-GYL-GIS (SEQ ID NO: 1260),

[0940] GAR-P04562WO16 Application (final) docx C-GIS-LAN (SEQ ID NO: 1261 ), and

[0941] C-GYR-GIT-LANWM (SEQ ID NO: 1262).

[0942] Very preferred are the following sequences: GYL-GIS (SEQ ID NO: 2),

[0943] YR-GIS-LANWM (SEQ ID NO: 4), YR-GIS-LANW (SEQ ID NO: 5),

[0944] GFR-GIS-LANWM (SEQ ID NO: 6), GYK-GIS-LANWM (SEQ ID NO: 7), GYR-GIS-LANWM (SEQ ID NO: 8), GYR-GYS-LANWM (SEQ ID NO: 9), GYR-GIT-LANWM (SEQ ID NO: 10), GYR-GIS-LAKWM (SEQ ID NO: 11 ) GYR-GIS-LANWV (SEQ ID NO: 12), GYL-GIS-LANW (SEQ ID NO: 13), GYR-GIS-LANWM-NH2(SEQ ID NO: 14) C-GYL-GIS (SEQ ID NO: 1260),

[0945] C-GIS-LAN (SEQ ID NO: 1261 ), and C-GYR-GIT-LANWM (SEQ ID NO: 1262).

[0946] Especially preferred is sequence GYRGISLANWM (SEQ ID NO: 8).

[0947] The present application is also directed to a hydrogel composition comprising an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one self-assembling peptide as disclosed herein, wherein the hydrogel is formed by non-covalent interactions of said self-assembling peptide in said aqueous dispersion phase.

[0948] Preferably the hydrogel compositions disclosed herein are hydrogel compositions, wherein the self-assembling peptide is present in said hydrogel at a level of from about 0.01 % by weight to about 10% by weight, based upon the total weight of the hydrogel.

[0949] Moreover it is preferred that wherein the aqueous dispersion medium is physiologically acceptable.

[0950] This aqueous dispersion medium preferably comprises one or more salts selected from (NH4)2SO4, Na2SO4, NaCI, KCI, CH3COONH4, NH3C(CH2OH)3CI, KH2PO4, and Na2HPO4.

[0951] GAR-P04562WO16 Application (final) docx The hydrogels disclosed herein have preferably a pH value between 4.0 and 8.5, more preferably between 4.5 and 8.0 or between 4.5 and 7.5 or between 4.5 and 7.0 or between 5.0 and 7.5 or between 5.0 and 7.0.

[0952] Moreover, the hydrogels disclosed herein have preferably an ionic strength between 0.0001 M and 1.5 M, preferably between 0.001 M and 0.5 M, more preferably 0.005 M and 0.3 M.

[0953] Furthermore, the hydrogels disclosed herein have preferably a storage modulus in the range of about 10 Pa to about 100,000 Pa.

[0954] The amino acids in the peptide chains may have any stereochemical orientation. For example, each amino acid may independently from each other be an L-amino acid or a D-amino acid. In one embodiment, all amino acids in the peptide chain are L-amino acids. In one embodiment, all amino acids in the peptide chain are D-amino acids.

[0955] The amino acids in the peptide chain may optionally be in their salt form. A person skilled in the art knows that this may depend, for example, on the environment of the peptide chain. For example, an acidic environment may lead to protonation of basic functional groups of the side chains of the amino acids. For example, a basic environment may lead to deprotonation of acidic functional groups of the side chains of the amino acids.

[0956] In preferred embodiments, the peptide chains form aggregates with each other.

[0957] In preferred embodiments, the peptide chains are self-assembling. Without wishing to be bound by theory: The peptide chains may form non-covalent bonds with each other. The peptide chains may form a supramolecular assembly. This may lead to non-covalent or supramolecular crosslinking, which may lead to gelation. In one embodiment, the peptide chains may form nanofibers or nanofibrillar structures. In one embodiment, the peptide chains may form beta sheets.

[0958] The peptide chains may optionally contain further amino acids. In further embodiments, at most 50%, preferably at most 40%, more preferably at most 30%, even more preferably at most 20%, even more preferably at most 10%, even more preferably at most 5%, particularly preferably at most 2%, of the amino acids in the

[0959] GAR-P04562WO16 Application (final) docx peptide chain are further amino acids. In other embodiments, the peptide chains do not contain any further amino acids. Preferably, the further amino acids are amino acids other than proteinogenic amino acids. Preferably, the further amino acids are selected from fluorine-containing amino acids, hydroxy group-containing amino acids other than proteinogenic amino acids, boronic acid-containing amino acids, anthracenyl-containing amino acids, amino acids having C2-C10 alkyl groups other than proteinogenic amino acids, amino acids having C2-C10 alkenyl groups, and amino acids having C2-C10 alkynyl groups. Preferably, the further amino acids F are selected from azidohomoalanine, acridinylalanine, phenylselenocysteine, sulfoserine, p-iodophenylalanine, bipyridylalanine, dansylalanine, o-nitrobenzyl cysteine, 7- nitroindolinyl-amino acids, propargylglycine, azidonorleucine, 5-bromotryptophan, L- 4’-deoxy-4’-iodophenylalanine, tetrazine alanine, dipyridyl tetrazine serine, hydroxyproline, beta-alanine, citrulline, ornithine, norleucine, 3-nitrotyrosine, nitroarginine, and pyroglutamic acid.

[0960] Description of the Figures

[0961] Figure 1: shows TEM images of the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at pH 4.75 (100 mM acetate buffer). A: 10 mg / mL. B: 1 mg / mL. TEM grid of 10 mg / mL sample was most densly covered amongst all samples

[0962] Figure 2: shows TEM images of the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at pH 7.4 (DPBS). A: 10 mg / mL. B: 1 mg / mL.

[0963] Figure 3: shows TEM images of the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at pH 8 (100 mM phosphate buffer). A: 10 mg / mL. B: 1 mg / mL. TEM images of GYRGISLANWM peptide at pH 8 (100mM phosphate buffer). Left: 10 mg / mL. Right: 1 mg / mL. At 1 mg / mL, no fibrils were observed at all.

[0964] Figure 4: Rheological characterization of hydrogels comprising the inventive selfassembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at 10 mg / mL (1 wt%) in 100 mM acetate buffer, pH 4.75. Analyses include A time sweep measurement for monitoring of gelation kinetics,

[0965] GAR-P04562WO16 Application (final) docx B strain sweep for monitoring gel-to-sol transition and shear thinning behavior, C frequency sweep to examine potential frequency dependent mechanical properties, as well as D consecutive time and strain sweep to analyze thixotropic behavior and gel recovery, with a comparative demonstration of gel formation during initial sample gelation and during recovery after gel-to-sol transition in the strain sweep E.

[0966] Figure 4B: Crossover-Strain for gel-to-sol transition is found to be 141%.

[0967] Figure 4D: Gel recovery after about 800s is around 34%.

[0968] Figure 5: Rheological characterization of hydrogels comprising the inventive selfassembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at 10 mg / mL (1 wt%) in DPBS, pH 7.4. Analyses include A time sweep measurement for monitoring of gelation kinetics, B strain sweep for monitoring gel-to-sol transition and shear thinning behavior, C frequency sweep to examine potential frequency dependent mechanical properties, as well as D consecutive time and strain sweep to analyze thixotropic behavior and gel recovery, with a comparative demonstration of gel formation during initial sample gelation and during recovery after gel-to-sol transition in the strain sweep E.

[0969] Figure 5B: Crossover-Strain for gel-to-sol transition is found to be 9.6%.

[0970] Figure 5D: Gel recovery after about 800s is around 8%.

[0971] Figure 6: Rheological characterization of hydrogels comprising the inventive selfassembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at 10 mg / mL (1 wt%) in phosphate buffer 100mM, pH 8. Analyses include A time sweep measurement for monitoring of gelation kinetics, B strain sweep for monitoring gel-to-sol transition and shear thinning behavior, C frequency sweep to examine potential frequency dependent mechanical properties, as well as D consecutive time and strain sweep to analyze thixotropic behavior and gel recovery, with a comparative demonstration of gel formation during initial sample gelation and during recovery after gel-to-sol transition in the strain sweep E.

[0972] Figure 6B: Crossover-Strain for gel-to-sol transition is found to be 0.5%.

[0973] Figure 6D: Gel recovery after about 800s is around 70%.

[0974] Figure 7: Rheological characterization of hydrogels comprising the inventive selfassembling peptide with the sequences (A) CGYLGIS (SEQ ID NO: 1260), (B) CGISLAN (SEQ ID NO: 1261 ), and (C) CGYRGITLANWM (SEQ ID NO: 1262) at 2 wt% and 1 wt%, respectively. Measurements include a time sweep at 0.3% strain (left panel) and a thixotropy examination performed by a consecutive strain sweep followed by a

[0975] GAR-P04562WO16 Application (final) docx time sweep (0.3%) (right panel); TEM images of the inventive selfassembling peptides with the sequences (D) CGYLGIS (SEQ ID NO: 1260), (E) CGISLAN (SEQ ID NO: 1261 ), and (F) CGYRGITLANWM (SEQ ID NO: 1262) at pH 7.4 (left image) and pH 2 (right image), 1 mg / mL; rheological characterization of hydrogels comprising the inventive self-assembling peptide with the sequences (G) CGYLGIS (SEQ ID NO: 1260), (H) CGISLAN (SEQ ID NO: 1261 ), and (I) CGYRGITLANWM (SEQ ID NO: 1262) at 2 wt% and 1 wt%, respectively, by strain sweep measurement.

[0976] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

[0977] Further modifications and alternative embodiments of various aspects of the invention will be apparent to those skilled in the art in view of this description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the general manner of carrying out the invention. It is to be understood that the forms of the invention shown and described herein are to be taken as examples of embodiments. Elements and materials may be substituted for those illustrated and described herein, parts and processes may be reversed, and certain features of the invention may be utilized independently, all as would be apparent to one skilled in the art after having the benefit of this description of the invention. Changes may be made in the elements described herein without departing from the spirit and scope of the invention as described in the following claims.

[0978] GAR-P04562WO16 Application (final) docx EXAMPLES

[0979] Abbreviations and Acronyms

[0980] DPBS - Dulbecco’s Phosphate Buffered Saline

[0981] Methods

[0982] Synthesis

[0983] The peptides were synthesized according to methods known in the art. All used amino acids are L-amino acids.

[0984] If not stated otherwise, RT refers to room temperature (20 - 25°C).

[0985] Sample preparation:

[0986] Dissolving solid powder directly in respective solvent:

[0987] The peptide solid was dissolved directly in the respective solvent to yield a 1 mg / ml or 10 mg / mL solution / suspension or hydrogel. For example, 1 mg peptide solid was dissolved in 1 mL buffer (e.g., DPBS, pH 7.4) and mixed via vortex for approx. 5s to yield a 1 mg / mL solution / suspension. The sample was then incubated on a shaker at 500 rpm (22°C) for 24 h. To yield a 10 mg / mL hydrogel, 10 mg peptide solid were dissolved in 1 mL buffer (e.g., DPBS, pH 7.4) and mixed via vortex or pipetting for approx. 3s and incubated until gelation was completed or until further use with immediate start of gelation upon mixing with buffer.

[0988] Transmission electron microscopy (TEM):

[0989] TEM was performed with aliquots of preincubated peptide samples. In order to assess the sample structures at 10 mg / mL, a dilution from 10 mg / mL was performed prior to imaging. The peptide was dissolved at 10 mg / mL in sterile filtered (0.22 pm filter unit) i) 100 mM acetate buffer pH 4.75, ii) DPBS pH 7.4, or iii) 100mM phosphate buffer pH 8 and after 1 hour incubation at room temperature diluted to 1 mg / mL in the respective solvent i-iii. For example, 0.17 mg of peptide were dissolved in 17 pL of the solvent i) to yield a 10 mg / mL solution / hydrogel. From this stock solution, 2 pL were transferred to 20 pL of solvent i) to yield a 1 mg / mL solution. 10 pL of the sample (a) 10 mg / mL as well as b) 1 mg / mL) were deposited on a copper grid coated with a thin electron-transparent Formvar-layer (Figures 1 to 3). Alternatively, 5 pL of the sample (1 mg / mL) at either pH 7 or pH 2, as indicated in

[0990] GAR-P04562WO16 Application (final) docx Figure 7, were deposited on a copper grid coated with a thin electron-transparent Formvar-layer (Figure 7). Subsequent to an incubation time of 5 min, the sample solution was removed using filter paper, approx. 5 pL of an aqueous 4% uranyl acetate solution were added on a surface and the copper grid layed on top and left for incubation for 2.5 minutes to enhance sample contrast via staining. The grids were washed three times in Milli-Q-water, excess water was removed via filter paper and the grids were dried in air. Imaging was performed in high vacuum with a JEOL 1400 transmission electron microscope at an acceleration voltage of 120 kV equipped with a CCD camera.

[0991] Rheology:

[0992] Rheological characterization was conducted using a DHR3 rheometer (TA Instruments) equipped with a temperature controller and a solvent reservoir to prevent hydrogel drying. Experiments were performed using an 8 mm parallel-plate geometry with hydrogels of approximately 30 pL volume resulting in a gap size of approximately 0.5 mm. Characterization of the hydrogel mechanical properties was conducted at 25 °C. Gels were prepared directly on the plate by adding buffer to the lyophilized peptide to achieve 20 mg / mL (2wt%) or 10 mg / mL using DPBS pH 7.4, 100 mM phosphate buffer pH 8, or 100mM acetate buffer pH 4.75.

[0993] Different experiments were performed:

[0994] (i) Time sweep: oscillatory time-sweep measurements were performed to monitor the gelation curves at a fixed strain of 0.1 % or 0.3% and a fixed frequency of 1 Hz at 25°C until gelation was complete.

[0995] (ii) Strain sweep: Oscillatory strain sweeps (0.01-1000%) were conducted at a fixed frequency of 1 Hz at 25°C.

[0996] (iii) Frequency sweeps: Frequency sweeps (0.01-100 rad / s) were performed at a fixed strain of 0.1 % at 25°C.

[0997] (iv) Thixotropy measurement: Consecutive measurements of an oscillatory strain sweep (0.01-1000%) at 25°C with a fixed frequency of 1 Hz followed by an oscillatory time sweep measurement with a fixed strain of 0.1 % or 0.3% and frequency of 1 Hz for 800 s or 1000 s at 25°C were conducted to analyze the self-healing capacity of the hydrogels. In this context, the hydrogel recovery at the end of the consecutive oscillatory time sweep (e.g. 0.1 % strain, 800s) was analyzed comparing G’ after the amplitude sweep with G’ prior to it.

[0998] GAR-P04562WO16 Application (final) docx -=ABK

[0999] Example 1

[1000] The self-assembling peptide of amino acid sequence GYRGISLANWM (SEQ ID NO: 8) was prepared and analyzed in accordance with the above described methods.

[1001] (SEQ ID NO: 8)

[1002] Results: The TEM results are demonstrated in Figures 1 -3. Figure 1 shows TEM images of the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at pH 4.75 (100 mM acetate buffer). A: 10 mg / mL. B: 1 mg / mL. TEM grid of 10 mg / mL sample was most densly covered amongst all samples. Figure 2 shows TEM images of the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at pH 7.4 (DPBS). A: 10 mg / mL. B: 1 mg / mL. Figure 3 shows TEM images of the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at pH 8 (100 mM phosphate buffer). A: 10 mg / mL. B: 1 mg / mL. TEM grid of 10 mg / mL At 1 mg / mL, no fibrils were observed at all. The results to the rheological characterization of hydrogels are demonstrated in Figures 4 -6. Figure 4 shows rheological characterization of hydrogels comprising the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at 10 mg / mL (1 wt%) in 100 mM acetate buffer, pH 4.75. Analyses include A time sweep measurement for monitoring of gelation kinetics, B strain sweep for monitoring gel-to-sol transition and shear thinning behavior, C frequency sweep to examine potential frequency dependent mechanical properties, as well as D consecutive time and strain sweep to analyze thixotropic behavior and E gel recovery after shear stress. Figure 5 shows Rheological characterization of hydrogels comprising the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at 10 mg / mL (1 wt%) in DPBS, pH 7.4. Analyses include A time

[1003] GAR-P04562WO16 Application (final) docx sweep measurement for monitoring of gelation kinetics, B strain sweep for monitoring gel-to-sol transition and shear thinning behavior, C frequency sweep to examine potential frequency dependent mechanical properties, as well as D consecutive time and strain sweep to analyze thixotropic behavior and E gel recovery after shear stress. Figure 6 shows rheological characterization of hydrogels comprising the inventive self-assembling peptide with the sequence GYRGISLANWM (SEQ ID NO 8) at 10 mg / mL (1 wt%) in 100mM phosphate buffer, pH 8. Analyses include A time sweep measurement for monitoring of gelation kinetics, B strain sweep for monitoring gel-to-sol transition and shear thinning behavior, C frequency sweep to examine potential frequency dependent mechanical properties, as well as D consecutive time and strain sweep to analyze thixotropic behavior and E gel recovery after shear stress.

[1004] Example 2

[1005] In addition to the self-assembling peptide of amino acid sequence GYRGISLANWM (SEQ ID NO: 8) of Example 1 , further peptides have been analyzed (in accordance with the Methods as described above). The peptides are shown in table 1 .

[1006] Gelation behavior

[1007] Table 1 Peptide screening for gelation in DPBS at 1 wt%.

[1008] GAR-P04562WO16 Application (final) docx

[1009] *C - Terminal: Amidation n / a: insoluble

[1010] Example 3

[1011] In addition to the peptides capable of forming a hydrogel by self-assembly of amino acid sequences of Example 1 and Example 2, further peptides have been analyzed (in accordance with the Methods as described above). The peptides are shown in table 2.

[1012] Table 2 Peptide screening for gelation in DPBS at 1 wt% and 2 wt% (weight percent).

[1013] The TEM results are demonstrated in Figure 7. Figure 7 shows TEM images of the inventive self-assembling peptide with the sequences CGYLGIS (SEQ ID NO 1260), CGYRGITLANWM (SEQ ID NO; 1261 ), CGISLAN (SEQ ID NO: 1262) at 1 mg / mL at pH 7.4 (DPBS) or at pH 2 (0.1 % TFA in water).

[1014] The results to the rheological characterization of hydrogels are demonstrated in Figure 7. Figures 7A to 7C show rheological characterization of hydrogels comprising the inventive self-assembling peptide with the sequences CGYLGIS (SEQ ID NO 1260), CGYRGITLANWM (SEQ ID NO 1261 ), CGISLAN (SEQ ID NO 1262) at 10 mg / mL (1 wt%) or 20 mg / mL (2 wt%) at pH 7 (DPBS). Analyses include a time sweep measurement at 0.3% strain for monitoring of gelation kinetics, strain sweep for monitoring gel-to-sol transition and shear thinning behavior, as well as consecutive time and strain sweep measurements to analyze thixotropic behavior with gel recovery after shear stress.

[1015] GAR-P04562WO16 Application (final) docx

Claims

Claims1 . A peptide capable of forming a hydrogel by self-assembly, wherein the peptide consists of 6 to 12 amino acids and having the following amino acid sequence of general formula (I):X1-A4-A5-A6-X2(I) whereinX1represents -H, C-, A3-, C-A3-, A2-A3- , C-A2-A3-, A1-A2-A3-, or C-A1-A2-A3-; wherein C represents the amino acid cysteine;X2represents -H, -A7, -A7-A8, -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11;A1and A4represent independently of each other a small neutral amino acid or a neutral hydrophilic amino acid;A2and A5represent independently of each other a neutral amino acid, an aromatic amino acid or an amino acid amide;A3represents a basic amino acid, a large neutral amino acid, or an amino acid amide;A6represents an amino acid selected from S, T, C, N, Q, Y, A, G, and V;A7and A8represent independently of each other a neutral amino acid;A9represents a basic amino acid, or an amino acid amide;A10represents a basic amino acid, or an aromatic amino acid;A11represents a neutral amino acid, a hydrophilic amino acid, or an amino acid amide.

2. The peptide according to claim 1 , whereinA1represents an amino acid selected from G and A;A2represents an amino acid selected from Y, F, and W;A3represents an amino acid selected from C, R, K and L;A4represents an amino acid selected from G, and A;A5represents an amino acid selected from I, Y, Q, N, L, and F;A6represents an amino acid selected from S, T, C, N, and Y;A7represents an amino acid selected from L, I, and V;A8represents an amino acid selected from A, G, and V;A9represents an amino acid selected from K, N, and Q;A10represents an amino acid selected from W, and F;A11represents an amino acid selected from M, M-NH2, L, I, V, A, and G.GAR-P04562WO16 Application (final) docx3. The peptide according to claim 1 , whereinA1represents an amino acid selected from G and A;A2represents an amino acid selected from Y, and F;A3represents an amino acid selected from R, K and L;A4represents an amino acid selected from G, and A;A5represents an amino acid selected from I, and Y;A6represents an amino acid selected from S and T;A7represents an amino acid selected from L, and I;A8represents an amino acid selected from A, and G;A9represents an amino acid selected from K and N;A10represents an amino acid selected from W, and F;A11represents an amino acid selected from M, M-NH2, L, I, and V.

4. The peptide according to claim 1 , whereinA1represents G;A2represents an amino acid selected from Y, and F;A3represents an amino acid selected from R, K and L;A4represents G;A5represents an amino acid selected from I, and Y;A6represents an amino acid selected from S and T;A7represents L;A8represents A;A9represents an amino acid selected from K and N;A10represents W;A11represents an amino acid selected from M, M-NH2, and V.

5. The peptide according to any one of the claims 1 to 4, whereinX1represents C-A1-A2-A3- , A1-A2-A3- , C-A2-A3- or A2-A3- ; and X2represents -A7-A8-A9, -A7-A8-A9-A10, or -A7-A8-A9-A10-A11.

6. The peptide according to claim 1 consisting of the following amino acid sequence selected from: GYLGIS (SEQ ID NO: 2), GISLAN (SEQ ID NO: 3), YRGISLANWM (SEQ ID NO: 4), YRGISLANW (SEQ ID NO: 5), GFRGISLANWM (SEQ ID NO: 6), GFRGISLANWV (SEQ ID NO: 312), GFRGISLANWM-NH2 (SEQ ID NO: 313), GYKGISLANWM (SEQ ID NO: 7), GYKGISLANWV (SEQ ID NO: 314), GYKGISLANWM-NH2 (SEQ ID NO: 315), GYRGYSLANWM (SEQ ID NO: 9), GYRGYSLANWV (SEQ ID NO: 316),GAR-P04562WO16 Application (final) docxGYRGYSLANWM-NH2 (SEQ ID NO: 317), GYRGITLANWM (SEQ ID NO: 10), GYRGITLANWV (SEQ ID NO: 318), GYRGITLANWM-NH2 (SEQ ID NO: 319), GYRGISLAKWM (SEQ ID NO: 11 ) GYRGISLAKWV (SEQ ID NO: 320) GYRGISLAKWM-NH2 (SEQ ID NO: 321 ) GYRGISLANWM (SEQ ID NO: 8), GYRGISLANWV (SEQ ID NO: 12), GYLGISLANW (SEQ ID NO: 13), and GYRGISLANWM-NH2 (SEQ ID NO: 14), CGYLGIS (SEQ ID NO: 1260), CGISLAN (SEQ ID NO: 1261 ), CGYRGITLANWM (SEQ ID NO: 1262), CYRGISLANWM (SEQ ID NO: 1263), CYRGISLANW (SEQ ID NO: 1264), CGFRGISLANWM (SEQ ID NO: 1265), CGYKGISLANWM (SEQ ID NO: 1266), CGYRGISLANWM (SEQ ID NO: 1267), CGYRGYSLANWM (SEQ ID NO: 1268), C GYRGISLAKWM (SEQ ID NO: 1269) CGYRGISLANWV (SEQ ID NO: 1270), CGYLGISLANW (SEQ ID NO: 1271 ), and CGYRGISLANWM-NH2 (SEQ ID NO: 1272).

7. The peptide according to claim 1 having the following amino acid sequence:GYL-GIS (SEQ ID NO: 2),GIS-LAN (SEQ ID NO: 3) YR-GIS-LANWM (SEQ ID NO: 4), YR-GIS-LANW (SEQ ID NO: 5), GFR-GIS-LANWM (SEQ ID NO: 6), GYK-GIS-LANWM (SEQ ID NO: 7), GYR-GIS-LANWM (SEQ ID NO: 8), GYR-GYS-LANWM (SEQ ID NO: 9), GYR-GIT-LANWM (SEQ ID NO: 10), GYR-GIS-LAKWM (SEQ ID NO: 11 ) GYR-GIS-LANWV (SEQ ID NO: 12), GYL-GIS-LANW (SEQ ID NO: 13), GYR-GIS-LANWM-NH2 (SEQ ID NO: 14) C-GYL-GIS (SEQ ID NO: 1260),C-GIS-LAN (SEQ ID NO: 1261 ), and C-GYR-GIT-LANWM (SEQ ID NO: 1262).

8. A hydrogel composition comprising an aqueous dispersion phase comprising an aqueous dispersion medium; and at least one peptide according to any one of the claims 1 to 7, wherein the hydrogel is formed by non-covalent interactions of said peptide in said aqueous dispersion phase.GAR-P04562WO16 Application (final) docx9. The hydrogel composition according to claim 8, wherein the peptide is present in said hydrogel at a level of from about 0.01 % by weight to about 10% by weight, based upon the total weight of the hydrogel.

10. The hydrogel composition according to claim 8 or 9 wherein the aqueous dispersion medium is physiologically acceptable.11 . The hydrogel composition according to any one of the claims 8 to 10, wherein the aqueous dispersion medium comprises one or more salts selected from (NH4)2SO4, Na2SO4, NaCI, KCI, CH3COONH4, NH3C(CH2OH)3CI, KH2PO4, and Na2HPO4.

12. The hydrogel according to any one of the claims 8 to 11 having a pH value between 4.0 and 8.5, preferably between 4.5 and 8.0.

13. The hydrogel according to any one of the claims 8 to 12 having an ionic strength between 0.0001 M and about 1.5 M.

14. The hydrogel according to any one of the claims 8 to 13 having a storage modulus in the range of about 10 Pa to about 100,000 Pa.GAR-P04562WO16 Application (final) docx

Images