N-Amino peptide-derived beta-sheet mimics

N-氨基肽衍生的 β-折叠模拟物

基本信息

批准号：
1709927
负责人：
Juan Del Valle
金额：
$ 41.81万
依托单位：
University of South Florida
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2020-03-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709927&HistoricalAwards=false
关键词：
Amino peptide derived beta sheet

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor Juan Del Valle from the University of South Florida. The project is an investigation of a new class of modified peptides that mimic protein structure. Proteins are the workhorses of the cell, and interactions between proteins govern many biological processes. The ability to modify these interactions with designed molecules (peptides) has been a long-standing challenge in chemistry. Professor Del Valle's work focuses on the mimicry of beta-sheets. This is a protein structure that is notoriously difficult to study due its tendency to clump together (aggregate). This research provides a toolkit for generating stable and aggregation-resistant mimics of the protein beta sheets. The project is also providing graduate and undergraduate students with rigorous training in laboratory research and scientific communication. The project is linked to the Tampa Preparatory School in an outreach effort providing internships to high school students. This research project integrates molecular design, chemical synthesis, conformational analysis, and biological studies to fully characterize the properties of backbone-aminated peptides. The Del Valle laboratory recently established methods to prepare C-alpha-substituted N-amino peptides (NAPs) through conventional solid-phase peptide synthesis. This project develops optimal synthetic protocols toward cyclic, macrocyclic, and polyaminated NAP variants for bi-facial beta-strand mimicry. The motifs are evaluated in model systems for their specific effects on beta-sheet stability and self-association using a combination of nuclear magnetic resonance spectroscopy, circular dichroism, and X-ray diffraction. The discrete impact of NAP constraints on protease/serum stability and passive membrane permeability relative to control peptides are being examined.

有了这个奖项，化学部门的化学过程计划是南佛罗里达大学的Juan del Valle教授的资助。该项目是对模仿蛋白质结构的新一类改性肽的研究。蛋白质是细胞的工作主场，蛋白质之间的相互作用控制了许多生物学过程。在化学方面，改变与设计分子（肽）的相互作用的能力一直是一个长期的挑战。德尔·瓦尔（Del Valle）教授的作品着重于beta表的模仿。这是一种蛋白质结构，众所周知，由于其趋势将其团结在一起（聚集）很难研究。这项研究提供了一种工具包，用于生成蛋白质β片的稳定和抗聚合的模仿。该项目还为研究生和本科生提供了实验室研究和科学交流方面的严格培训。该项目与坦帕预备学校有关，以推广工作为高中生提供实习。该研究项目集成了分子设计，化学合成，构象分析和生物学研究，以充分表征骨干固定的肽的特性。 Del Valle实验室最近建立了通过常规的固相肽合成来制备C-α取代的N-氨基肽（NAP）的方法。该项目为双种族β种模拟物开发了针对环状，大环和多酰化的NAP变体的最佳合成方案。在模型系统中评估了基序，以通过核磁共振光谱，圆形二色性和X射线衍射的结合来评估其对β-片稳定性和自我关联的特定影响。正在检查NAP约束对蛋白酶/血清稳定性和被动膜渗透性相对于对照肽的离散影响。