Stabilization of a polypeptide in non-aqueous solvents

被引：6

作者：

Wang, Wei ^{[1
]}

Martin-Moe, Sheryl ^{[1
]}

Pan, Clark ^{[1
]}

Musza, Laszlo ^{[1
]}

Wang, Y. John ^{[1
]}

机构：

[1] Bayer Healthcare, Berkeley, CA 94701 USA

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2008年 / 351卷 / 1-2期

关键词：

peptide stability; non-aqueous solvent; deamidation; zinc stabilization; dimerization; PACAP;

D O I：

10.1016/j.ijpharm.2007.09.012

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A pituitary adenylate cyclase-activating peptide (PACAP) analogue (HSDAVFTDNYTRLRKQVAAKKYLQSIKNKRY, P66) was formulated in several non-aqueous solvents in anticipation of improved shelf-life stability. However, the stability of this peptide in these solvents was found to be as poor as in an aqueous solution. The major degradation reaction in non-aqueous solvents was dimer formation. The proposed mechanism for dimerization was a nucleophilic attack of a basic amino acid on cyclic imide formed by dehydration or deamidation of Asp or Asn. Two approaches were found to be effective in stabilizing the peptide in non-aqueous solvents: (1) acidification of the peptide and (2) use of zinc chloride in the formulation. Stabilization could be attributed to reduction of the nucleophilicity of the reactive groups through protonation and metal-peptide interaction through chelation. The stabilization approaches are applicable only in a non-aqueous environment for this peptide, and possibly for other peptides with similar reactive moieties. (C) 2007 Elsevier B.V. All rights reserved.

引用

页码：1 / 7

页数：7

共 36 条

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