Amyloidogenicity and Aggregate Cytotoxicity of Human Glucagon-Like Peptide-1 (hGLP-1)

被引：19

作者：

Poon, S. ^{[1
]}

Birkett, N. R. ^{[1
]}

Fowler, S. B. ^{[2
]}

Luisi, B. F. ^{[3
]}

Dobson, C. M. ^{[1
]}

Zurdo, J. ^{[2
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[2] Zyentia Ltd, Cambridge CB22 3AT, England

[3] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

来源：

PROTEIN AND PEPTIDE LETTERS | 2009年 / 16卷 / 12期

关键词：

hGLP-1; protein aggregation; biopharmaceuticals; diabetes; amyloid fibrils; Alzheimer's disease; AMYLOID FIBRIL FORMATION; X-RAY-DIFFRACTION; NEURONAL DEGENERATION; THERAPEUTIC PEPTIDE; DIABETES-MELLITUS; GLOBULAR PROTEIN; SELF-ASSOCIATION; HUMAN CALCITONIN; HUMAN-DISEASE; SH3; DOMAIN;

D O I：

10.2174/092986609789839232

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The potential of human glucagon-like peptide-1 (hGLP-1) as a therapeutic agent is limited by its high aggregation propensity. We show that hGLP-1 forms amyloid-like structures that are preceded by cytotoxic aggregates, suggesting that aggregation of biopharmaceuticals could present a cytotoxic risk to patients besides the reported increased risk in immunogenicity.

引用

页码：1548 / 1556

页数：9

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