PREDOCTORAL FELLOWSHIP AWARDS FOR MINORITY STUDENTS

少数族裔学生的博士前奖学金

• 批准号: 2136519
• 负责人: ISAIAH IV PITTMAN
• 金额: $ 2.85万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2136519
• 关键词: PREDOCTORAL; FELLOWSHIP; AWARDS; MINORITY; STUDENTS

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.

我们的重点是检查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都通过 使用合成类似物。 研究是通过准备 与苯丙氨酸-324，苯丙氨酸-B25的替代的类似物 或在B链的C末端区域的色氨酸酪氨酸-B26 胰岛素。这些色氨酸残留物将随后用作探针 荧光光谱分析。可见的光谱分析 最初进行天然胰岛素以确定环己醇是否是 可以稳定一个特征时态以放松（t至r）构象 使用苯酚观察到的分子的变化。这个变化 由N末端的α-螺旋区的形成组成 与几何形状变化的B链结构域的发生 钴配位以六聚体形式的胰岛素形式中心。 实际上，环己醇确实证明是为了稳定这种转变，是 在相关实验中用于t转换的t 通过荧光光谱观察到含色氨酸的类似物。 有趣的是，观察到的构象变化也出现了 发生在类似物的单体形式中。进一步的研究将是 进行本地化和表征发生的结构变化 在胰岛素过渡到r过渡期间，并评估含义 胰岛素结构的生物作用。