Mecano growth factor peptides and their use

A growth factor, mechanical technology, applied in the direction of insulin-like growth factor, hormone peptide, specific peptide, etc., can solve the problem of expression decline and so on

Inactive Publication Date: 2008-11-05
UCL BUSINESS PLC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, Hill and Golds pink (2003) have demonstrated that in the rat tibialis anterior muscle, MGF is rapidly expressed in response to mech

Method used

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  • Mecano growth factor peptides and their use
  • Mecano growth factor peptides and their use
  • Mecano growth factor peptides and their use

Examples

Experimental program
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Example Embodiment

[0152] Preparation of polypeptides or extended polypeptides of the invention

[0153] Polypeptides or extended polypeptides of the invention can be prepared using standard techniques. In general, they can be obtained by standard peptide synthesis techniques and, if desired, appropriate chemical modifications of the resulting amino acid sequence (eg, pegylation). In the absence of D-form amino acids, polypeptides and extended polypeptides can also be obtained by standard techniques by recombinant expression in host cells from appropriate coding DNA.

[0154] Standard techniques can also be used to isolate and purify to any desired degree. The polypeptides or extended polypeptides of the present invention will generally be isolated or purified, in whole or in part. The preparation of the isolated polypeptide or extended polypeptide may be any preparation as long as the preparation contains the polypeptide or the extended polypeptide at a higher concentration than the preparati...

Example Embodiment

[0169] Example

[0170] 1. Peptides

[0171] 1.1 Peptides of Examples 2, 3, 4 and 6

[0172] The peptides used in Examples 2, 3, 4 and 6 had the sequence of SEQ ID NO: 15, wherein the arginine at the penultimate position of the native sequence (see SEQ ID NOs: 1, 2 and 27) was replaced by histidine and the N-terminus is covalently linked to a polyethylene glycol (PEG) derivative ( O'O-bis(2-aminopropyl) polyethylene glycol 1900) (Jeffamine), and C-terminal amidation to stabilize the native sequence.

Example Embodiment

[0174] The peptide of Example 5 was purchased from Alta Bioscience, Birmingham, UK and synthesized by standard techniques using a peptide synthesizer. These peptides are non-pegylated, free of L-D conversion and C-terminal amidated.

[0175] In addition, a peptide equivalent to the peptide in 1.1 above with the same L-D conversion but without pegylation was also tested for stability (see 5.2.3 below). This peptide is synthesized by standard techniques using a peptide synthesizer. The resulting product was purified by HPLC and analyzed by MALDI-MS.

[0176] 1.3 Peptide of Example 7

[0177] 1.3.1 Peptide of Example 7.1

[0178] The peptide of Example 7.1 has an 8 amino acid sequence, Gly-Ser-Thr-Phe-Glu-Glu-His-Lys (SEQ ID NO: 33), with modifications to improve stability. exist Figure 8 In the peptide referred to as DMGF in , stabilization can be achieved by N-terminal pegylation as described in 1.1 above. exist Figure 8 In a peptide called CMGF in , stabilization can ...

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Abstract

This invention relates to biologically active polypeptides derived from the E peptide that forms the C-terminus of the insulin-like growth factor I (IGF-I) splice variant known as mechano growth factor (MGF). These peptides are modified to improve their stability compared to the naturally occurring E peptide.

Description

technical field [0001] The present invention relates to biologically active polypeptides derived from the E-domain forming the C-terminus of the mechano growth factor (MGF) known as a splice variant of insulin-like growth factor I (IGF-I) . These peptides have been modified to increase their stability compared to naturally occurring E domain peptides Background technique [0002] Mammalian IGF-I polypeptides have many isoforms that arise as a result of alternative mRNA splicing. In general, there are two types of isoforms, hepatic isoforms and non-hepatic isoforms. Hepatic isoforms may be expressed in the liver or other organs, but if expressed in other organs, are also equivalent to those isoforms expressed in the liver. The hepatic isoform has systemic effects and is the predominant isoform in mammals. Non-hepatic isoforms are less common and some are believed to have autocrine / paracrine effects. The MGF isoforms involved in the present invention are the latter. [0...

Claims

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Application Information

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IPC IPC(8): C07K14/65A61K38/30
CPCC07K14/65A61K38/00A61P1/04A61P3/10A61P9/00A61P9/04A61P9/10A61P11/00A61P13/02A61P17/02A61P21/00A61P21/04A61P25/00A61P25/16A61P25/28A61P25/32A61P29/00A61P31/18A61P35/00Y02A50/30
Inventor 杰弗里·戈德斯宾克杨士钰P·戈德斯宾克
Owner UCL BUSINESS PLC
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