Novel n-substituted polyglycine lipids

Abstract

The present invention relates to a compound of formula (I) or (II) or (III), wherein Y1, Y2, Y3, and Y4 are selected from -O-, -NH- and -S-, R1, R2, R6, and R10 are each selected from the groups consisting of -C10-C30 alkyl, -C10- C30 alkenyl, -C(=O)-C9-C29 alkyl or -C(=O)-C9-C29 alkenyl, R9 is selected from the group consisting of -C1-C3-alkyl, particularly R9 is -CH3, X is selected from -O-, -NMe- and -NH-, R3 is selected from -H, the group consisting of -C1-C3 alkyl, Z is selected from one of -NR11, and, R11 is selected from the groups consisting of -C1-C4 alkyl, -C1-C4 alkyl-NR7 2, - C1-C4 alkyl-OR7, wherein R7 is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl; R5 is selected from the group consisting of -C6-C12 alkyl, L is selected from any one of the moieties wherein R8 is selected from -H and the group consisting of -C1-C3 alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1; n is an integer in the range of 5 to 100.

Description

[0001]cor127wo Novel N-substituted Polyglycine Lipids Covalent molecule modification by polymers, especially PEGylation, which is the covalent attachment of polyethylene glycol (PEG) [H(OCH2CH2)nOH] chains to a molecule, has been the main approach for improving the efficacy of biotherapeutics. It is a widely employed and fast-growing technology that fulfils many of the properties required for drugs based on proteins and peptides. Overall, PEGylation renders molecules more robust and, especially for molecules with a greater volume, prolongs their residence time in the body; generally, the longer the PEG chain, the longer the elimination half-life of the PEG-protein conjugate. However, PEGylation with regular PEGs suffer from many drawbacks. First, as polymers of ethylene oxide, regular PEGs are always polydisperse mixtures and contain toxic side products. Furthermore, when the PEG chains are covalently bound to the molecule, the physicochemical characteristics are altered, resulting in changes in biological and consequently pharmacological properties. These changes are typically observed in receptor binding affinity, in vitro and in vivo biological activity, absorption rate and bioavailability, biodistribution, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles. It should be noted that once PEGylated the nature of the compound is largely altered and it may therefore behave as a different molecule. Polysarcosines are known in polymer science for almost a century and one of the most prevalent representatives of the polypeptoids. They are non-ionic but hydrophilic, and highly biocompatible. Polysarcosine or pSar / polySar combines PEG-like properties, e.g., excellent solubility in water, protein resistance, low cellular toxicity and a non-immunogenic character, while being based on endogenous material. Polysarcosines can reduce protein adsorption on surfaces, may effectively prevent aggregation of nanoparticles in complex body fluids and can shield sensitive bioactive agents from degradation. Although degradation and metabolism of the polypeptoid are not yet understood, pSar seems to avoid acute immune responses and acute toxicity, which all together indicates that pSar may be more than just an alternative to PEG. First examples of polysarcosine containing lipids have already been utilized in the literature. These products are non-uniform and feature a polydispersity index (PDI) >1 since they are generally produced via nucleophilic ring-opening polymerization of amino acid N-carboxyanhydrides (NCA). This leads to a non-homogenous mixture of compounds with different chain lengths, which in turn show different physicochemical properties. Thus, their structure and activities cannot be determined clearly. The disadvantages of these compounds are for example, severe difficulties in purification, unpredictable pharmacokinetic properties, cor127wo bioavailability, and accumulation in organs, disadvantages similar to known PEGylated compounds. This leads to difficulties in drug clinical application and regulatory approval. [1, 2, 3] Based on the above-mentioned state of the art, the objective of the present invention is to provide novel polypeptoid lipids, which are easy to purify and characterise and potentially simplify the regulatory approval and drug clinical application, and provide a controllable chain length and enhanced stability, particularly when used in drug delivery vehicles. This objective is attained by the subject-matter of the independent claims of the present specification, with further advantageous embodiments described in the dependent claims, examples, figures and general description of this specification. Summary of the Invention A first aspect of the invention relates to a compound of formula (I) or (II) or (III) Y1, Y2, Y3, and Y4are selected from -O-, -NH- and -S-, R1, R2, R6, and R10are each selected from the groups consisting of -C10-C30alkyl, -C10- C30alkenyl, -C(=O)-C9-C29alkyl or -C(=O)-C9-C29alkenyl, R9is selected from the group consisting of -C1-C3-alkyl, particularly R9is -CH3, X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3 alkyl, , cor127wo R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl; R5is selected from the group consisting of -C6-C12 alkyl, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1, n is an integer in the range of 5 to 100. Terms and definitions General For purposes of interpreting this specification, the following definitions will apply and whenever appropriate, terms used in the singular will also include the plural and vice versa. In the event that any definition set forth below conflicts with any document incorporated herein by reference, the definition set forth shall control. The terms “comprising”, “having”, “containing”, and “including”, and other similar forms, and grammatical equivalents thereof, as used herein, are intended to be equivalent in meaning and to be open-ended in that an item or items following any one of these words is not meant to be an exhaustive listing of such item or items, or meant to be limited to only the listed item or items. For example, an article “comprising” components A, B, and C can consist of (i.e., contain only) components A, B, and C, or can contain not only components A, B, and C but also one or more other components. As such, it is intended and understood that “comprises” and similar forms thereof, and grammatical equivalents thereof, include disclosure of embodiments of “consisting essentially of” or “consisting of.” Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure. cor127wo Reference to “about” a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X.” As used herein, including in the appended claims, the singular forms “a”, “or” and “the” include plural referents unless the context clearly dictates otherwise. "And / or" where used herein is to be taken as specific recitation of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as "A and / or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone). The term uniform in the context of the present specification relates to a monodisperse compound, characterised in that the compound is homogenous and has a defined structure, wherein the vast majority of molecules have the same number of repeating units or relative molecular mass. A monodisperse or uniform compound has a low PDI and / or a high chain length purity. The uniform character or monodispersity of a compound is defined through the polydispersity index and / or the chain length purity. The term polydispersity index (PDI) in the context of the present specification relates to a measure of broadness of molecular weight distribution. The larger the PDI, the broader the molecular weight distribution. The PDI of a compound is calculated as the ratio of weight average molecular weight (Mw), wherein w is the weight average, by number average molecular weight (Mn), wherein n is the number average (PDI = MW / Mn). A compound with 100% uniform character or monodispersity would equal a PDI of 1.00. A monodisperse or uniform compound has a low PDI, in particular in a range in between 1.000 and 1.005, more particularly in a range between 1.000 and 1.003. The term chain length purity in the context of the present specification relates to the percentage of compound having an identical chain length n, within the entirety of structurally related compounds formed. The chain length purity thereby refers to the relative abundance of a specific oligomer or polymer chain length compared to the total amount of all chain lengths present. It is particularly relevant in low-dispersity samples and can be used to assess the precision of polymer synthesis. The chain length purity is calculated as the ratio of the amount of formed compound with chain length n to the sum of the amount of all compounds formedcontaining a structurally related polymeric chain (purity of chain length n =Nn = amount of chain length n). The result is given as a percentage. A monodisperse or uniform compound cor127wo has a high chain length purity of at least 80%, in particular of at least 90 %, more particularly 95 %. Any patent document cited herein shall be deemed incorporated by reference herein in its entirety. The formulae of the present specification follow the convention of organic chemistry to not show hydrogen atoms on carbon scaffolds. Carbon is tetravalent and bonds not shown are assumed to be hydrogen unless shown otherwise. The term alkyl in the context of the present specification relates to a saturated linear, or branched, wherein in certain embodiments one carbon-carbon bond may be unsaturated. The term C1-C3 alkyl in the context of the present specification relates to a saturated linear or branched hydrocarbon having 1, 2, or 3 carbon atoms. Non-limiting examples for a C1-C3 alkyl are methyl, ethyl, propyl, prop-2-enyl. In certain embodiments, a C1-C3 alkyl is a methyl, ethyl, or propyl. The term C1-C4 alkyl in the context of the present specification relates to a saturated linear or branched hydrocarbon having 1, 2, 3 or 4 carbon atoms. Non-limiting examples for a C1-C4 alkyl are methyl, ethyl, propyl, prop-2-enyl, n-butyl, 2-methylpropyl, tert-butyl, cyclo-butyl, cyclo-propyl, methyl-cyclo-propyl. In certain embodiments, a C1-C4 alkyl is a methyl, ethyl, propyl or butyl moiety. A C6-C12 alkyl in the context of the present specification relates to a saturated linear or branched hydrocarbon having 6, 7, 8, 9, 10, 11 or 12 carbon atoms. Non-limiting examples for a C6-C12 alkyl include hexyl, heptyl, 6-methylheptan-2-yl, 5,6-dimethylheptan-2-yl, 6,7- dimethyloct-4-en-2-yl, 5-ethyl-6-methylheptan-2-yl, octyl, nonyl, decyl, undecyl, dodecyl, 2- methyloctanyl, 3-methylpentyl, 3-ethyl-2,2-dimethylhexanyl, 3-ethylhexanyl or 3,6- dimethyloctane. A C10-C30 alkyl in the context of the present specification relates to a saturated linear or branched hydrocarbon having 10 to 30 carbon atoms. The definition of saturated linear hydrocarbon also applies to C10-C20alkyl, C9-C29alkyl, and C9-C19alkyl. The term alkenyl in the context of the present specification relates to a hydrocarbon comprising 2 or more double bonds. Unsubstituted alkenyl is of formula -CH=CH- when being located intramolecularly, and of formula -CH=CH2when being a terminal moiety. An alkenyl consists of C and H only. A C10-C30alkenyl in the context of the present specification relates to an unsaturated linear or branched hydrocarbon having 10 to 30 carbon atoms, wherein the C10-C30alkenyl in the context of the present specification may contain 2 to 15 unsaturated carbon-carbon bonds. cor127wo The definition of unsaturated linear hydrocarbon also applies to C9-C29alkenyl, C10-C20alkenyl, and C9-C19alkenyl. Where used in the context of chemical formulae, the following abbreviations may be used: Me is methyl CH3, Et is ethyl -CH2CH3, Prop is propyl –(CH2)2CH3 (n-propyl, n-pr) or -CH(CH3)2 (iso-propyl, i-pr), but is butyl -C4H9, -(CH2)3CH3, -CHCH3CH2CH3, -CH2CH(CH3)2 or -C(CH3)3. Detailed Description of the Invention A first aspect of the invention relates to a compound of formula (I) or (II) or (III) Y1, Y2, Y3, and Y4are selected from -O-, -NH- and -S-, R1, R2, R6, and R10are each selected from the groups consisting of -C10-C30alkyl, -C10- C30alkenyl, -C(=O)-C9-C29alkyl or -C(=O)-C9-C29alkenyl, R9is selected from the group consisting of -C1-C3-alkyl, X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3alkyl, , R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3alkyl or -C(=O)-C1-C3alkyl; R5is selected from the group consisting of -C6-C12alkyl, L is selected from any one of the moieties cor127wo wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1, n is an integer in the range of 5 to 100. Attaching the glycerol-like building block at the N-terminus of the sarcosine instead of the C- terminus allows for the full lipopeptide to be synthesised directly on the resin, thereby simplifying purification of the product. Furthermore, varying Y1and Y2in formula (I) affects the stability of the N-substituted polyglycine containing lipopeptide, particularly when used in LNP. Varying Y1and Y2and / or R1and R2allows to control the stability and biodegradability of the N-substituted polyglycine containing lipopeptide. Additionally, the core structure can be varied using a variety of readily available enantiomerically pure amino acid building blocks, allowing facile and quick customisation of the compounds fulfilling steric requirements of the N- substituted polysarcosine. In turn, fulfilling steric requirements has a direct effect on the performance of N-substituted polysarcosine containing drug delivery vehicles, in particular liquid nanoparticles (LNP). Furthermore, the variation of Z allows tuning of the hydrophilicity depending on the needs. Hydrophilicity has a direct influence on the flexibility of the LNP membrane and therefore on the fusion with cellular membranes and successful endosomal escape. In certain embodiments, the compound is uniform. The uniform or monodisperse compounds of the present invention provide several advantages to known Poly-Sar compounds. Known Poly-Sar compounds are prepared through polymerisation leading to a non-homogenous mixture of compounds with different chain lengths, which in turn show different physicochemical properties. Thus, their structure and activities cannot be determined clearly. The disadvantages of these compounds are for example, severe difficulties in purification, unpredictable pharmacokinetic properties, bioavailability, and accumulation in organs. This leads to difficulties in drug clinical application and regulatory approval. The use of polysarcosines provided by a stepwise solid-phase synthesis yields uniform compounds. These are predictable in their chemical structure, biological activity and thus easy to purify and analyse. They furthermore have predictable cor127wo pharmacokinetic properties and bioavailability and are thus compatible for use as biopharmaceuticals. In certain embodiments, the is of formula (I) or (II) or (III) Y1, Y2, Y3, and Y4are selected from -O-, and -NH- R1, R2, R6, and R10are each selected from the groups consisting of -C10-C30alkyl, -C10- C30alkenyl, -C(=O)-C9-C29alkyl or -C(=O)-C9-C29alkenyl, R9is selected from the group consisting of -C1-C3-alkyl, particularly R9is -CH3,X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3alkyl, Z is selected from one of -NR11, wherein R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3alkyl or -C(=O)-C1-C3alkyl; R5is selected from the group consisting of -C6-C12alkyl, L is selected from any one of the moieties , wherein R8is selected from -H and the group consisting of -C1-C3alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1, n is an integer in the range of 5 to 100. In certain embodiments, the compound is of formula (II) or (III) cor127wo wherein Y1, Y2, Y3, and Y4are selected from -O-, -NH- and -S-, R6, and R10are each selected from the groups consisting of -C10-C30alkyl, -C10-C30alkenyl, -C(=O)-C9-C29alkyl or -C(=O)-C9-C29alkenyl, R9is selected from the group consisting of -C1-C3-alkyl, R4is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, -C1-C4alkyl- OR7, wherein R7is independently selected from -H, and the groups consisting of -C1- C3 alkyl or -C(=O)-C1-C3 alkyl, X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3alkyl, , R11is selected from the groups consisting of -C1-C4 alkyl, -C1-C4 alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3alkyl or -C(=O)-C1-C3alkyl; R5is selected from the group consisting of -C6-C12 alkyl, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1, n is an integer in the range of 5 to 100. cor127wo In certain embodiments, p is 0.Compounds with p being 0, therefore having a CH group at this point show improved formation of drug delivery vehicles, in particular LNP if used herein. In certain embodiments, q is an integer in the range of 1 to 4. In certain embodiments, q is an integer in the range of 1 to 3. In certain embodiments, q is 1. In certain embodiments, Y1, Y2, Y3, and Y4are selected from -O-, and -NH-. In certain embodiments, Y1, Y2, and Y3, are selected from -NH-, -O-, and -S-. In certain embodiments, Y1, Y2, and Y3, are selected from -O-, and -S-. In certain embodiments, Y1, and Y2are -O-. In certain embodiments, Y3is -O-. In certain embodiments, Y4is -NH- or -O-. In certain embodiments, Y4is -NH- In certain embodiments, R1, R2, R6, and R10are independently selected from the groups consisting of -C10-C20 alkyl, -C10-C20 alkenyl, -C(=O)-C9-C19 alkyl, or -C(=O)-C9-C19 alkenyl. Compounds having a lipid length of -C10-C20 alkyl or -C9-C19 alkenyl show a good stability and allow a good cellular uptake and can interfere with the interaction of cationic lipid and mRNA, when used in drug delivery vehicles, in particular LNPs. In certain embodiments, R1and R2are independently selected from the groups consisting of - C10-C20 alkyl, -C10-C20 alkenyl, -C(=O)-C9-C19 alkyl, or -C(=O)-C9-C19 alkenyl. In certain embodiments, R1and R2are independently selected from the groups consisting of - C10-C20 alkyl, or -C(=O)-C9-C19 alkyl. Compounds containing a -O(C=O)- group within Y1-R1 or Y2-R2 have a high biodegradability as they can be degraded by esterases. Compounds containing an ether group -O- within Y1-R1or Y2-R2do show a higher stability towards enzyme induced degradation. In certain embodiments, R1and R2are independently selected from the groups consisting of - C10-C15alkyl, or -C(=O)-C9-C14alkyl. In certain embodiments, R1, R2, R6, and R10are selected from the groups consisting of -C(=O)- C9-C19alkyl or -C(=O)-C9-C19alkenyl. In certain embodiments, R6, and R10are independently selected from the groups consisting of -C10-C20alkyl, -C10-C20alkenyl, -C(=O)-C9-C19alkyl, or -C(=O)-C9-C19alkenyl. cor127wo In certain embodiments, R6and R10are selected from the groups consisting of -C(=O)-C9-C19alkyl or -C(=O)-C9-C19alkenyl. In certain embodiments, R6and R10are selected from the group consisting of -C(=O)-C9-C19 alkyl. In certain embodiments, X-R3is selected from -OMe, -NMe2, and -NH2. In certain embodiments, X-R3is selected from -OH and -NH2. In certain embodiments, X-R3is -NH2. In certain embodiments, R5is selected from the group consisting of -C7-C10 alkyl. In certain embodiments, R9is -CH3. In certain embodiments, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, and m is an integer in the range of 1 and 3. In certain embodiments, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3alkyl, and m is an integer in the range of 1 and 3. In certain embodiments, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3alkyl, and m is an integer in the range of 1 and 3. In certain embodiments, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, and cor127wo m is an integer in the range of 1 and 3. In certain embodiments, L is selected from any one of the moieties , wherein R8is selected from -H and the group consisting of -C1-C3alkyl, and m is an integer in the range of 1 and 3. In certain embodiments, L is selected from any one of the moieties , wherein R8is selected from -H and the group consisting of -C1-C3alkyl In certain embodiments, R8is selected from -H and -CH3. In certain embodiments, In certain embodiments, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3 alkyl. In certain embodiments, L is , wherein R8is selected from -H and the group consisting of -C1-C3 alkyl. In certain embodiments, wherein R8is -H. In certain embodiments, Z is selected from - NR11-, , and R11is selected from the groups consisting of -C1-C4 alkyl, -C1-C4 alkyl-NR72, -C1-C4 alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl. cor127wo In certain embodiments, Z is selected from - NR11-, and R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, -C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl. In certain embodiments, Z is selected from - NR11-, and R11is selected from the groups consisting of -C1-C4 alkyl, -C1-C4 alkyl-NR72, -C1-C4 alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl. In certain embodiments, Z is selected from - NR11-, and R11is selected from the group consisting of -C1-C4 alkyl. In certain embodiments, Z is selected from - NR11-, and R11is selected from the group consisting of -C1-C2 alkyl. Alkyl residues of this length provide improved hydrophilicity to function as solubiliser. In certain embodiments, Z is selected from any one of the moieties . In certain embodiments, Z is selected from any one of the moieties . In certain embodiments, Z is selected from any one of the moieties . In certain embodiments, Z is selected from any one of the moieties cor127wo . In certain embodiments, Z is selected from any one of the moieties . In certain embodiments, Z is selected from any one of the moieties . In certain embodiments, Z is selected from any one of the moieties In any one . In certain embodiments, n is an integer in the range of 5 to 80. In certain embodiments, n is an integer in the range of 5 to 50.In certain embodiments, n is an integer in the range of 10 to 50. In certain embodiments, n is an integer in the range of 7 to 40. In certain embodiments, n is an integer in the range of 10 to 30. In certain embodiments, n is an integer in the range of 10 to 20. In certain embodiments, q is an integer in the range of 1 to 6. In certain embodiments, the compound has a poly dispersity index of less than 1.01. In certain embodiments, the compound has a poly dispersity index of less than 1.008. In certain embodiments, the compound has a poly dispersity index of less than 1.005. In certain embodiments, the compound has a poly dispersity index of less than 1.003. cor127wo In certain embodiments, the compound has a chain length purity higher than 50%. In certain embodiments, the compound has a chain length purity higher than 60%. In certain embodiments, the compound has a chain length purity higher than 70%. In certain embodiments, the compound has a chain length purity higher than 80%. In certain embodiments, the compound has a chain length purity higher than 80%. In certain embodiments, the compound has a chain length purity higher than 90%. In certain embodiments, the compound has a chain length purity higher than 95%. In certain embodiments, the compound is PEG free. In certain embodiments, the compound is of formula (I) or (II) or (III) Y1, Y2, Y3, and Y4are selected from -O-, -NH- and -S-, R1, R2, R6, and R10are each selected from the groups consisting of -C10-C20alkyl, -C10- C20alkenyl, -C(=O)-C9-C19alkyl or -C(=O)-C9-C19alkenyl, R9is -CH3, X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3alkyl, Z is selected from one of -NR11, wherein R11is selected from the groups consisting of -C1-C2 alkyl, -C1-C4 alkyl-NR72, - C1-C4 alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl; R5is selected from the group consisting of -C6-C12 alkyl, L is selected from any one of the moieties cor127wo wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1, n is an integer in the range of 5 to 100. In certain embodiments, the compound is of formula (I) or (II) or (III) Y1, Y2, Y3, and Y4are selected from -O-, and -NH-, R1, R2, R6, and R10are each selected from the groups consisting of -C10-C20alkyl, -C10- C20alkenyl, -C(=O)-C9-C19alkyl or -C(=O)-C9-C19alkenyl, R9is CH3, X is selected from -O-, and -NH-, R3is H, Z is selected from one of -NR11, wherein R11is selected from the groups consisting of -C1-C2 alkyl, -C1-C4 alkyl-NR72, - C1-C4 alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl; R5is selected from the group consisting of -C6-C12 alkyl, L is selected from any one of the moieties wherein R8is selected from -H and the group consisting of -C1-C3 alkyl; cor127wo q is an integer in the range of 1 to 4, p is 0 or 1, n is an integer in the range of 7 to 40. In certain embodiments, the compound is of formula (I) or (II) or (III) Y1, Y2, Y3, and Y4are selected from -O-, and -NH-, R1, R2, R6, and R10are each selected from the groups consisting of -C10-C20alkyl, -C10- C20alkenyl, -C(=O)-C9-C19alkyl or -C(=O)-C9-C19alkenyl, R9is CH3, X is selected from -O-, and -NH-, R3is H, Z is selected from one of the moieties R5is selected from the group consisting of -C8-C10 alkyl, L is selected from any one of the moieties q is an integer in the range of 1 to 4, p is 0 or 1, n is an integer in the range of 7 to 40. In certain embodiments, the compound is of formula (III) cor127wo wherein Y3, and Y4are selected from -O-, -NH- and -S-, R6, and R10are each selected from the groups consisting of -C10-C20alkyl, -C10-C20alkenyl, -C(=O)-C9-C19alkyl or -C(=O)-C9-C19alkenyl, R9is CH3, X is selected from -O-, and -NH-, R3is -H, Z is selected from one of -NR11, R11is selected from the groups consisting of -C1-C2alkyl, -C1-C4alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl; q is an integer in the range of 1 to 4, p is 0 or 1, n is an integer in the range of 7 to 40. The invention is further illustrated by the following examples and figures, from which further embodiments and advantages can be drawn. These examples are meant to illustrate the invention but not to limit its scope. Examples Example 1: General preparation of H-Sarn-NH2 via Solid Phase Peptide Synthesis H2N sieber resin1Fmoc-removal Deprotection 20 vol-% piperidine in DMF (7 mL / gresin), 3 x 10 min per treatment Wash with DMF Coupling Fmoc-AA-OH Coupling 2.0 eq. Fmoc-AA-OH, 3.0 eq. DIC, 2.0 eq. Oxymapure®, 90 min cor127wo Wash with DMF Final Wash with IPA and MTBE After the final wash, the resin was dried in vacuo to constant weight. Example 2: General preparation of H-AA-Sarn-NH2via Solid Phase Peptide Synthesis Fmoc-removal Deprotection 20 vol-% piperidine in DMF (7 mL / gresin), 3 x 10 min per treatment Wash with DMF Coupling Fmoc-AA-OH Coupling 2.0 eq. Fmoc-AA-OH, 3.0 eq. DIC, 2.0 eq. Oxymapure®, 90 min Wash with DMF Final Wash with IPA and MTBE After the final wash, the resin was dried in vacuo to constant weight. Example 3: Coupling of fatty acids to obtain FA-AA(FA)-Sarn-NH2 A solution of a fatty acid (FA) (6.0 eq.) and 4-dimethylaminopyridine (DMAP) (0.3 eq.) in DMF / DCM 1:1 (10 mL / gresin) was prepared. N,N'-Diisopropylcarbodiimide (DIC) (3.0 eq.) was added to the solution. The prepared solution was immediately added to the H-AA-Sarn-NH2- peptidyl resin and the mixture was shaken for 24 h at room temperature. The resin was filtered off and subsequently washed with DMF (4×), DCM (4×), IPA (4×) and MTBE (4×). After the final wash, the resin was dried in vacuo to constant weight. cor127wo Example 4: Coupling of Cholesteryl chloroformate to obtain Cholesterol-Sarn-NH2 A solution of triethylamine (3.0 eq.) in DCM (1.2M) was added to a H-Sarn-NH2-peptidyl resin. Subsequently a solution of cholesterol chloroformate (10 eq.) in DCM (4.0M) was added to the H-Sarn-NH2-peptidyl resin. The mixture was shaken for 16 h at room temperature. The resin was filtered off and subsequently washed with DCM (4×), IPA (4×) and MTBE (4×). After the final wash, the resin was dried in vacuum to constant weight. Example 5: Cleavage from sieber resin The peptidyl resin was consecutively treated with 1% trifluoroacetic acid (TFA) in dichloromethane (DCM) for 10 min for five times (10 Veq. per treatment). After each treatment the cleavage solution was added to a solution of 10% pyridine in acetonitrile [5×2 Veq. (related to the volume of the cleavage solution)]. The combined solutions were concentrated under reduced pressure to remove the DCM. The lipopeptide solution was purified via MPLC. The resulting solution was lyophilized to yield a colorless powder. Example 6: Cleavage from rink resin cor127wo The peptidyl resin was consecutively treated with TFA / H2O 95:5 (10 Veq.) for 1 h. The cleavage solution was added to diisopropyl ether [10 Veq. (related to the volume of the cleavage solution)]. The originating precipitate was washed, dried and purified via MPLC. The resulting solution was lyophilized to yield a colorless powder. Example 7: General preparation of H-Sarn-NH2 via submonomer Synthesis Bromoacetylation step Bromoacetylation 10 eq. Bromoacetic acid in DMF (0.8 M), 10 eq. DIC in DMF (0.8 M), 20 min Wash with DMF Substitution step Substitution 13 eq. Amine in DMF (1.0 M), 60 min Wash with DMF Final Wash with IPA and MTBE After the final wash, the resin was dried in vacuo to constant weight. Example 8: General preparation of Trt-AA-Sarn-NH2 via Solid Phase Peptide Synthesis Fmoc-removal Deprotection 20 vol-% piperidine in DMF (7 mL / gresin), 3 x 10 min per treatment Wash with DMF Coupling Fmoc-AA-OH Coupling 2.0 eq. Fmoc-AA-OH / Fmoc-AA(Trt)-OH, 3.0 eq. DIC, 2.0 eq. Oxymapure®, 90 min Wash with DMF Final Wash with IPA and MTBE After the final wash, the resin was dried in vacuo to constant weight. cor127wo Example 9: Coupling of fatty acids to obtain asymmetric substituted FA1-AA(FA2)-Sarn-NH2 A solution of the corresponding fatty acid (FA1) (2.0 eq.) and 4-dimethylaminopyridine (DMAP) (0.3 eq.) in DMF / DCM 1:1 (10 mL / gresin) was prepared. N,N'-Diisopropylcarbodiimide (DIC) (3.0 eq.) was added to the solution. The prepared solution was immediately added to the TrtO- AA-Sarn-NH2-peptidyl resin and the mixture was shaken for 24 h at room temperature. The resin was filtered off and subsequently washed with DMF (4×), DCM (4×), IPA (4×) and MTBE (4×). After the final wash, the resin was dried in vacuo to constant weight. The protecting group was removed by treatment with TFA / H2O / TIS (98:1:1) for 3x 10min (10 mL / gresin). The resin was filtered off and subsequently washed with DMF (4×) and DCM (4×). A solution of the corresponding fatty acid (FA2) (2.0 eq.) and 4-dimethylaminopyridine (DMAP) (0.3 eq.) in DMF / DCM 1:1 (10 mL / gresin) was prepared. N,N'-Diisopropylcarbodiimide (DIC) (3.0 eq.) was added to the solution. The prepared solution was immediately added to the HO-AA(FA1)-Sarn- NH2-peptidyl resin and the mixture was shaken for 24 h at room temperature. The resin was filtered off and subsequently washed with DMF (4×), DCM (4×), IPA (4×) and MTBE (4×). After the final wash, the resin was dried in vacuo to constant weight. Peptide batch Exact Nr. m(is Overall conjugated lipid size olated) yield mass / m / z theory m / z found u 1 Myr-Ser(Lau)- 14 H2 150 µmol 6 768.4610 Sar -N 7 mg 30 % 1491.88 [M+2Na]2+768.4602 Myr-Ser(Myr)- 1044.7043 2 Sar7-NH2 150 µmol 48 mg 32% 1021.72 1 [M+Na]+144.7040 3 Myr-Ser(Myr)- 150 µmol 150 782.4767 Sar14-NH2 mg 66 % 1519.94 [M+2Na]2+782.4762 4 Myr-Ser(Myr)- 1137. Sar71-NH2197 µmol 285 mg 26 % 5571.44 0086 [M+5Na]5+1137.0048 5 Pal-Ser(Pal)- 4-NH2150 µmol 1 810.5080 Sar174 mg 74 % 1576.05 [M+2Na]2+810.5076 6 Ste-Ser(Ste)- 150 µmol 157 mg 64 % 1632.1 838.5393 Sar14-NH25 [M+2Na]2+838.5381 7 Ole-Ser(Ole)- 150 µmol 844.5106 Sar14-NH2141 mg 58 % 1628.12 [M+Na+K]2+844.5091 8 Lau-Ser(Lau)- 199 µmol 120 mg 42 % 1463. 754.4454 Sar14-NH2 83 [M+2Na]2+754.4452 cor127wo 9 Lau-Ser(Lau)- 150 µmol 156 mg 42 % 2458 1252.2069 Sar28-NH2.94 [M+2Na]2+1252.1991 10 Myr-Ser(Myr)- 1280.23 28 2 150 µmol 141 mg 37 % 2515.0 82 Sar -NH 4 [M+2Na]2+1280.238811 Pal-Ser(Pal)- Sar28-NH2 150 µmol 178 mg 46 % 2571.15 1308.2695 [M+2Na]2+1308.270612 Ste-Ser(Ste)- 1 1336.3008 Sar28-NH2 50 µmol 68 mg 17 % 2627.26 [M+2Na]2+1336.303013 Ole-Ser(Ole)- Sar28-NH2150 µmol 74 mg 19 % 2623.23 1334.2851 [M+2Na]2+1334.286714 Myr-Dpr(Myr)- 200 µmol 20 781.9847 Sar14-NH27 mg 68 % 1518.95 [M+2Na]2+781.985015 Myr-Lys(Myr)- 14 2 200 µmol 180 mg 5 803.0082 Sar -NH 8 % 1561.03 [M+2Na]2+803.007816 Myr-Thr(Myr)- 200 µmol 130 mg 42 % 15 789.4845 Sar14-NH2 33.96 [M+2Na]2+789.484117 Myr-Dhp(Myr)- 782.968 2 200 µmol 100 mg 33 % 1520.92 7 Sar14-NH [M+2Na]2+782.968418 Myr-Ser(Myr)- Sar7-NH2150 µmol 76 mg 49 % 1022.38 1044.7043 [M+Na]+1044.703919 Lau-Ser(Ste)- 269 µmol 8 796.4923 Sar14-NH28 mg 21 % 1547.99 [M+2Na]2+796.4902 Cen-Ser(Ole)- 1018.82 20 Sar7-NH2 200 µmol 126 mg 62 % 1017.68 1018. [M+54 +H] Ole-Ser(Ole)- 1130.82 21 Sar7-NH2 200 µmol 118 mg 51 % 1129.81 113 [M+H]+0.71 Trd-Ser(Cap)- 974.63 22 Sar7-NH2 200 µmol 155 mg 72% 951.64+974.50 [M+Na] Ste-Ser(Cap)- 1258.26 23 Sar28-NH2200 µmol 164 mg 32% 2513.49 1 [M+2H]2+258.33 Cap-Ser(Trd)- 1375.26 25Sar71-NH2200 µmol 243 mg 12% 5498.011376.14 [M+4H]4+Ste-Ser(Pal)- 1885.74 26 Sar71-NH2 200 µmol 120 mg 5.3% 5652.18 [M+3H]3+1886.11 Pal-Ser(Cap)- 1386.52 27 Sar71-NH2 200 µmol 53 mg 2.5% 5540.06 [M+44+1386.66 H] Trd-Ser(Ste)- 1404.55 28 Sar71-NH2 200 µmol 132 mg 6.1% 5610.14 140 [M+4H]4+4.16 Cen-Ser(Ole)- 1392.52 29 Sar71-NH2200 µmol 119 mg 6.0% 5564.05 [M+4H]4+1392.65 Cen-Ser(Cen)- 1364.49 30 Sar71-NH2200 µmol 218 mg 15% 5451.93 [M+4H]4+1364.6631 Myr-Ser(Myr)- 750 µmol 173 mg 15 % 1519.9 782.4767 EtNAcGly7-NH2 4 [M+2Na]2+782.4749 Myr-Ser(Myr)- 1519.98 32 EtNAcGly7-NH2 750 µmol 174 mg 15% 1518.97 [M+H]+1519.68 cor127wo Myr-Ser(Myr)- 1843.33 33 EtGly12-NH2750 µmol 240 mg 17% 1842.32 [M+H]+1843.33 Myr-Ser(Myr)- 1546.09 34 EtGly12-NH2 750 µmol 4 mg 0.3% 1545.08 1546.98 [M+H]+Myr-Ser(Myr)- 1284.37 35 EtGly24-NH2 750 µmol 51 mg 2.6% 2565.72 128 [M+22+4.48 H] Myr-Ser(Myr)- 1258.26 36 EtNAcGly14-NH2 750 µmol 86 mg 4.6% 2513.49 [M+2H]2+1258.29 Myr-Ser(Myr)- 1561.04 37 EtOMeGly9-NH2750 µmol 121 mg 10% 1560.03 [M+H]+1560.96 Myr-Ser(Myr)- 1299.31 38 EtOMeGly18-NH2750 µmol 35 mg 1.8% 2595.60+1299.38 [M+H] Cholesterol-CO- 927,63 39 Sar7-NH2 400 µmol 170 mg 44% 926.62 [M+H]+927.42 40 Cholesterol-CO- 7 ar14-NH2 200 µmol 101 mg 34.9294 S 35 % 1423.88 [M+2Na]2+734.9288 Cholester 1825.34 41 ol-CO- Sar71-NH2400 µmol 116 mg 4% 5473.00 182 [M+3H]3+6.12 di-Tet-glyc-CO- 1522.04 42Sar14-NH2100 µmol 74 mg 45% 1521.031522.93 [M+H]+di-Myr-glyc-CO- 1550.00 43Sar14-NH2100 µmol 59 mg 38% 1548.991549.87 [M+H]+The abbreviations are to be understood as follows:Cap: capric acid Cen: 9-decenoic acid Lau: lauric acid Myr: myristic acid Pal: palmitic acid Ste: stearic acid Ole: oleic acid Trd: tridecanoic acid Dpr: 2,3-diaminopropionic acid Dhp: 2,3-dihydroxypropionic acid Example 10: Determination of PDI and chain length purity The polydispersity index (PDI) and chain length purity were determined using high resolution electrospray ionization mass spectrometry (HR-ESI MS). The relative abundance of different species (Ni) was determined based on the peak intensities in the HR-ESI MS spectrum, assuming that signal intensities correlate linearly with the number of ions detected. Only the cor127wo dominant ion species (typically the main peak such as [M+H]+or [M+Na]+) was considered for the analysis to ensure consistency. The number average molecular weight (Mn) represents the average based on the number of molecules at each molecular weight and is calculated using the following equation: Mn = ΣNiMi / ΣNi where Ni is the number of molecules with a specific molecular weight Mi. The weight average molecular weight (Mw) accounts for the contribution of each molecular weight based on its mass and is given by: Mw = ΣNiMi² / ΣNiMi where Ni and Mi are defined as above. The polydispersity (PD), which reflects the width of the molecular weight distribution, is expressed as the ratio of Mw to Mn: PDI = Mw / Mn Chain Length Purity (CLP) refers to the relative abundance of a specific oligomer or polymer chain length compared to the total amount of all chain lengths present. It is particularly relevant in low-dispersity samples and can be used to assess the precision of polymer synthesis. CLP for a given chain length i can be calculated using the formula: CLP = (Ni / ΣNi) × 100% where Ni is defined as above. This value represents the percentage of chains that have the exact desired length within a polymer sample. HR-ESI MS measurements were performed under the following conditions: capillary voltage 4500V, nebulizer gas 0,9 bar, dry gas 4,0 L / min, and a dry temperature 200 °C; on a ESI-MS Bruker Impact II. Samples were dissolved in methanol. Cited prior art documents: [1] Son K, Ueda M, Taguchi K, Maruyama T, Takeoka S, Ito Y. Evasion of the accelerated blood clearance phenomenon by polysarcosine coating of liposomes. J Control Release.2020 cor127wo [2] Bleher S, Buck J, Muhl C, Sieber S, Barnert S, Witzigmann D, Huwyler J, Barz M, Süss R. Poly(Sarcosine) Surface Modification Imparts Stealth-Like Properties to Liposomes. Small. 2019 [3] Christian Muhl, Marcus Conrad, Dennis Unthan, Matthias Barz, Synthesis and characterization of bisalkylated polysarcosine-based lipopolymers, European Polymer Journal, 2019. All scientific publications and patent documents cited in the present specification are incorporated by reference herein.

Claims

cor127wo Claims 1. A compound of formula (I) or (II) or (III)Y1, Y2, Y3, and Y4are selected from -O-, -NH- and -S-, R1, R2, R6, and R10are each selected from the groups consisting of -C10-C30alkyl, -C10- C30alkenyl, -C(=O)-C9-C29alkyl or -C(=O)-C9-C29alkenyl, R9is selected from the group consisting of -C1-C3-alkyl, particularly R9is -CH3,X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3alkyl,, R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3alkyl or -C(=O)-C1-C3alkyl; R5is selected from the group consisting of -C6-C12alkyl, L is selected from any one of the moietieswherein R8is selected from -H and the group consisting of -C1-C3 alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6,cor127wo p is 0 or 1, n is an integer in the range of 5 to 100.

2. The compound according to claim 1 is of formula (I) or (II) or (III)Y1, Y2, Y3, and Y4are selected from -O-, and -NH- R1, R2, R6, and R10are each selected from the groups consisting of -C10-C30alkyl, -C10- C30alkenyl, -C(=O)-C9-C29alkyl or -C(=O)-C9-C29alkenyl, R9is selected from the group consisting of -C1-C3-alkyl, particularly R9is -CH3,X is selected from -O-, -NMe- and -NH-, R3is selected from -H, the group consisting of -C1-C3alkyl, Z is selected from one of -NR11, wherein R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl-NR72, - C1-C4alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3alkyl or -C(=O)-C1-C3alkyl; R5is selected from the group consisting of -C6-C12alkyl, L is selected from any one of the moieties, wherein R8is selected from -H and the group consisting of -C1-C3alkyl, m is an integer in the range of 1 to 16; q is an integer in the range of 1 to 6, p is 0 or 1, n is an integer in the range of 5 to 100.

3. The compound according to claim 1 or 2, wherein the compound is uniform.cor127wo 4. The compound according to any of the preceding claims, wherein R1, R2, R6, and R10are independently selected from the groups consisting of -C10-C20alkyl, -C10-C20alkenyl, -C(=O)-C9-C19 alkyl, or -C(=O)-C9-C19 alkenyl, 5. The compound according to any of the preceding claims, wherein R1, R2, R6, and R10are selected from the groups consisting of -C(=O)-C9-C19 alkyl or -C(=O)-C9-C19 alkenyl.

6. The compound according to any of the preceding claims, wherein X-R3is selected from -OMe, -NMe2, and -NH2, particularly X-R3is selected from -OH and -NH2.

7. The compound according to any of the preceding claims, wherein R5is selected from the group consisting of -C7-C10 alkyl, 8. The compound according to any of the preceding claims, wherein L is selected from any one of the moietieswherein R8is selected from -H and the group consisting of -C1-C3 alkyl, and m is an integer in the range of 1 and 3.

9. The compound according to any of the preceding claims, wherein L is selected from any one of the moieties, wherein R8is selected from -H and the group consisting of -C1-C3 alkyl, and m is an integer in the range of 1 and 3.

10. The compound according to any of the preceding claims, wherein L is selected from any one of the moieties , wherein R8is selected from -H and the group consisting of -C1-C3 alkyl 11. The compound according to any of the preceding claims, wherein R8is selected from - H and -CH3.cor127wo 12. The compound according to any of the preceding claims, wherein Z is selected from - NR11-, and R11is selected from the groups consisting of -C1-C4alkyl, -C1-C4alkyl- NR72, -C1-C4 alkyl-OR7, wherein R7is independently selected from -H, and the groups consisting of -C1-C3 alkyl or -C(=O)-C1-C3 alkyl.

13. The compound according to any of the preceding claims, wherein Z is selected from - NR11-, and R11is selected from the groups consisting of -C1-C4 alkyl, in particular wherein Z is selected from - NR11-, and R11is selected from the groups consisting of - C1-C4 alkyl.

14. The compound according to any of the preceding claims, wherein Z is selected from any one of the moieties.

15. The compound according to any of the preceding claims, wherein Z is selected from one of the moieties.

16. The compound according to any of the preceding claims, wherein n is an integer in the range of 5 to 80, particularly wherein n is an integer in the range of 7 to 40.

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