SUBSTITUTED ALKENE ISOSTERE DIPEPTIDE PEPTIDOMIMETICS

取代的烯烃等排二肽模拟肽

• 批准号: 2414423
• 负责人: TODD C HENNINGER
• 金额: $ 1万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2414423
• 关键词: alkenes; conformation; dipeptides; peptide analog; peptide chemical synthesis

The purpose of the proposed research is to explore new synthetic pathways toward alkene dipeptide peptidomimetics and to explore their conformational properties. The new mimics will include highly substituted alkenes, including mimics of proline-containing dipeptides. The choice of alkene substituents has been guided by molecular modeling. Specifically, the isosteres will be synthesized by nti-SN2' cuprate additions to alkenyl aziridines prepared by asymmetric aza-glycid ester condensations. Subsequently, and extension of this methodology to phosphonate and boronate analogs will be investigated and substituted alkene isostere mimics of the Ala-Ser dipeptide will be incorporated into mimics of the M and R cleavage sites of assemblin, an important regulator of human cytomegalovirus maturation.

这项研究的目的是探索新的合成途径 对烯烃二肽肽模拟物，并探讨其构象 特性. 新的模拟物将包括高度取代的烯烃， 包括含脯氨酸二肽的模拟物。 烯烃的选择 取代基已经由分子建模指导。 具体而言是 电子等排体将通过nti-SN 2 '铜酸盐加成到烯基上来合成。 通过不对称的氮杂-缩水甘油酯缩合制备的氮杂环丙烷。 随后，将这种方法扩展到膦酸盐和硼酸盐 类似物将被研究，取代的烯烃电子等排体模拟物的 将Ala-Ser二肽掺入M和R切割的模拟物中 人巨细胞病毒的重要调节因子--聚集蛋白的位点 成熟