Polypeptides selective for av ss3 integrin conjugated with a variant of human serum albumin (HSA) and pharmaceutical uses thereof

A technology of human serum albumin and integrin, applied in the field of treatment and prevention of avβ3 integrin-related diseases, can solve the problem of reducing polypeptide activity and achieve high selectivity

Inactive Publication Date: 2012-05-23
NAT CHENG KUNG UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, peptides linked to HSA may be prone to aggregation of disulfide linkages, especially under acidic conditions, leading to the formation of intermolecular dimers
When these polypeptides are administered to mammals, the formation of intermolecular dimers can reduce the activity of the polypeptides and / or lead to immunogenicity

Method used

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  • Polypeptides selective for av ss3 integrin conjugated with a variant of human serum albumin (HSA) and pharmaceutical uses thereof
  • Polypeptides selective for av ss3 integrin conjugated with a variant of human serum albumin (HSA) and pharmaceutical uses thereof
  • Polypeptides selective for av ss3 integrin conjugated with a variant of human serum albumin (HSA) and pharmaceutical uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0183] Construction of the gene encoding HSA(C34S)-ARLDDL

Embodiment 1A

[0185] Construction of a gene encoding HSA(C34S)-ARLDDL by overlap extension PCR and ligation reaction

[0186] Take HSA (invitrogen clone ID: IOH23065) was used as a template to construct the HSA C34S gene. The C34S mutation was generated by two-step polymerase chain reaction (PCR). The first step of PCR was performed using sense primers containing C34S mutation sites and antisense primers containing KpnI, SacII restriction enzyme sites and TAA terminators. A second-step PCR was performed using a sense primer containing a BstI restriction site and a secretion signal peptide, and an antisense primer containing a KpnI, SacII restriction site and a TAA terminator. The secretion signal sequence of HSA propeptide, alpha factor propeptide derived from Saccharomyces cerevisiae, or a fusion protein of HSA propeptide and alpha factor propeptide can be used for the expression of secreted protein. Structural gene ARLDDL was amplified by PCR using a sense primer containing a KpnI r...

Embodiment 1B

[0188] Construction of a gene encoding HSA(C34S)-ARLDDL by gene synthesis

[0189] DNA encoding the secretion signal peptide sequence HSA(C34S)-ARLDDL was synthesized. The secretion signal sequence of HSA propeptide, alpha factor propeptide derived from Saccharomyces cerevisiae, or a fusion protein of HSA propeptide and alpha factor propeptide can be used for the expression of secreted protein. The resulting gene product was cloned into a yeast recombinant vector with appropriate restriction sites. Then the recombinant vector was transformed into Escherichia coli XL1-blue strain. Colonies were selected on agar plates containing low-salt LB (1% tryptone, 0.5% yeast extract, 0.5% NaCl, 1.5% agar, pH 7.0) and 25 μg / ml antibiotic Zocine. The Escherichia coli XL1-blue clone was selected, and the plasmid was isolated and sequenced.

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Abstract

The invention generally relates to fusion proteins comprising a rhodostomin variant having an RGD motif variant 48ARLDDL53, wherein the rhodostomin variant is conjugated with a variant of Human Serum Albumin (HSA). The invention also relates to the use of these fusion proteins for treatment and prevention of avss3 integrin-associated diseases.

Description

field of invention [0001] The present invention generally relates to fusion proteins comprising rhodostoxin variants comprising RGD motif variants 48 ARLDDL 53 , the rhodopsin variant is conjugated to a human serum albumin (HSA) variant. The present invention also relates to the treatment and prevention of avβ3 integrin-related diseases with the fusion protein. Background of the invention [0002] Bone is a complex tissue composed of several cell types that continually undergoes a process of regeneration and repair known as "bone remodeling." The two main cell types responsible for bone remodeling are osteoclasts, which resorb bone, and osteoblasts, which form new bone. Bone remodeling is known to be regulated by several systemic hormones (eg, parathyroid hormone, 1,25-dihydroxyvitamin D3, sex hormones, and calcitonin) and local factors (eg, nitric oxide, prostaglandins, growth factors, and cellular factor) regulation. [0003] Integrins are heterodimeric matrix recepto...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00
CPCC07K14/70546A61K38/00A61P19/08A61P19/10A61P27/02A61P29/00A61P3/14A61P35/00A61P35/04A61P43/00C07K19/00C07K14/76C07K14/435A61K38/17
Inventor 庄伟哲符文美
Owner NAT CHENG KUNG UNIV
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