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对刺激敏感的丝弹性蛋白样蛋白嵌段共聚物的基因工程。

Genetic engineering of stimuli-sensitive silkelastin-like protein block copolymers.

作者信息

Nagarsekar Ashish, Crissman John, Crissman Mary, Ferrari Franco, Cappello Joseph, Ghandehari Hamidreza

机构信息

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, USA.

出版信息

Biomacromolecules. 2003 May-Jun;4(3):602-7. doi: 10.1021/bm0201082.

Abstract

Differentially charged analogues of block copolymers containing repeating sequences from silk (GAGAGS) and elastin (GVGVP) were synthesized using genetic engineering techniques by replacing a valine residue with glutamic acid. The sensitivity to pH and temperature was examined at various polymer concentrations, ionic strengths, and polymer lengths. The polymers transitioned from soluble to precipitate state over narrow temperature ranges. The transition temperature T(t) (the temperature at which half-maximal spectrophotometric absorption was observed) increased with increasing pH up to pH 7.0 and leveled off above this value for the Glu-containing polymer (17E)(11). T(t) was independent of pH for the Val-containing polymer (17V)(11). It decreased with increasing ionic strength, polymer concentration, and polymer length for both polymers. These results suggest that by substituting charged amino acids for neutral amino acids at strategic locations in the polymer backbone and by control of the length of silkelastin-like block copolymers using genetic engineering techniques, it is possible to precisely control sensitivity to pH, temperature, and ionic strength.

摘要

利用基因工程技术,通过用谷氨酸取代缬氨酸残基,合成了含有来自蚕丝(GAGAGS)和弹性蛋白(GVGVP)重复序列的带不同电荷的嵌段共聚物类似物。在不同的聚合物浓度、离子强度和聚合物长度下,研究了其对pH值和温度的敏感性。这些聚合物在狭窄的温度范围内从可溶状态转变为沉淀状态。转变温度T(t)(观察到最大分光光度吸收一半时的温度)随着pH值升高至7.0而升高,对于含谷氨酸的聚合物(17E)(11),在此值以上趋于平稳。对于含缬氨酸的聚合物(17V)(11),T(t)与pH值无关。两种聚合物的T(t)均随离子强度、聚合物浓度和聚合物长度的增加而降低。这些结果表明,通过在聚合物主链的关键位置用带电荷的氨基酸取代中性氨基酸,并利用基因工程技术控制类蚕丝弹性蛋白嵌段共聚物的长度,可以精确控制对pH值、温度和离子强度的敏感性。

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