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PREDOCTORAL FELLOWSHIP AWARDS FOR MINORITY STUDENTS

少数族裔学生的博士前奖学金

基本信息

批准号：
2545689
负责人：
ISAIAH IV PITTMAN
金额：
$ 3.39万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-10-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/2545689
关键词：
conformation insulin insulin receptor minority health professional peptide hormone analog protein structure function

项目摘要

Our focus is on examining the conformational changes that may occur in the insulin molecule, in both its hexameric and monomeric states, via the use of synthetic analogs. Research was undertaken by the preparation of analogs with the substitution of phenylalanine-324, phenylalanine-B25, or tyrosine-B26 by tryptophan in the C-terminal region of the B-chain of insulin. These tryptophan residues would later serve as probes for fluorescence spectroscopic analysis. Visible spectroscopic analysis of native insulin was initially undertaken to determine if cyclohexanol could stabilize a characteristic tense to relaxed (T to R) conformational change in the molecule that has been observed using phenol. This change consists of the formation of an alpha-helical region in the N-terminal B-chain domain that occurs concomitant with changes in the geometries of the cobalt coordination centers in the hexameric form of insulin. Cyclohexanol did in fact prove to stabilize this transformation and was used in related experiments in which the T to R transformation of tryptophan-containing analogs were observed by fluorescence spectroscopy. interestingly the conformational changes that were observed also appear to occur in the monomeric forms of the analogs. Further studies will be conducted to localize and characterize the structural changes occurring during the T to R transition of insulin, and evaluate the implications of insulin structure in its biologic actions.

我们的重点是研究可能发生的构象变化，胰岛素分子，在其六聚体和单体状态下，通过使用合成类似物。研究是由编写具有苯丙氨酸-324，苯丙氨酸-B25，或酪氨酸-B26在B链的C-末端区域被色氨酸取代，胰岛素这些色氨酸残基后来用作探针，荧光光谱分析可见光谱分析最初使用天然胰岛素来确定环己醇是否可以稳定一个特征性的紧张放松（T到R）构象在使用苯酚时观察到的分子变化。这种变化包括在N-末端形成α-螺旋区域， B链结构域，其伴随着胰岛素六聚体形式中的钴配位中心。环己醇事实上证明稳定了这种转化，在相关实验中使用，通过荧光光谱法观察到含葡聚糖的类似物。有趣的是，观察到的构象变化也出现在以类似物的单体形式存在。进一步的研究将进行定位和表征发生的结构变化在胰岛素的T到R转换期间，并评估其影响胰岛素结构在其生物学作用中的作用。