Chemical stability of peptides in polymers. 2. Discriminating between solvent and plasticizing effects of water on peptide deamidation in poly(vinylpyrrolidone).
Chemical stability of peptides in polymers. 2. Discriminating between solvent and plasticizing effects of water on peptide deamidation in poly(vinylpyrrolidone).
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聚合物中肽的化学稳定性。
DOI：
10.1021/js9802289
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发表时间：
1999
影响因子：
3.8
通讯作者：
Topp,EM
中科院分区：
文献类型：
--
作者：
Lai,MC;Hageman,MJ;Schowen,RL;Borchardt,RT;Laird,BB;Topp,EM
The mechanistic role of water in the deamidation of a model asparagine‐containing hexapeptide (Val‐Tyr‐Pro‐Asn‐Gly‐Ala) in lyophilized formulations containing poly(vinylpyrrolidone) (PVP) and glycerol was investigated. Glycerol was used as a plasticizer to vary formulation glass transition temperature (Tg) without significantly changing water content or activity. Increases in moisture and glycerol contents increased the rate of peptide deamidation. This increase was strongly correlated withTgat constant water content and activity, suggesting that increased matrix mobility facilitates deamidation. In rubbery systems (T>Tg), deamidation rates appeared to be independent of water content and activity in formulations with similarTgs. However, in glassy formulations with similarTgs, deamidation increased with water content, suggesting a solvent/medium effect of water on reactivity in this regime. An increase in water content also affected the degradation product distribution; less of the cyclic imide intermediate and more of the hydrolytic products, isoAsp‐ and Asp‐hexapeptides, were observed as water content increased. Thus, residual water appears to facilitate deamidation in these solid PVP formulations both by enhancing molecular mobility and by solvent/medium effects, and also participates as a chemical reactant in the subsequent breakdown of the cyclic imide.
