New Strategies for Peptide Mimicry

肽模拟的新策略

• 批准号: 10667594
• 负责人: Caroline Proulx
• 金额: $ 36.29万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667594
• 关键词: Adopted; Biological; Biological Products; Derivation procedure; Development; Goals; Hormones; Libraries; Methods; Molecular Conformation; N-substituted Glycines; Neurotransmitters; Peptide Hydrolases; Peptide Library; Peptides; Peptoids; Research; Structure; Structure-Activity Relationship; Surface; Therapeutic; antimicrobial; conformer; design; improved; mimicry; monomer; novel; peptide analog; peptidomimetics; programs; protein protein interaction; response; scaffold; screening; small molecule; tool

ABSTRACT Our research program is focused on the development of new broadly applicable tools for peptide mimicry. Peptides are an important class of compounds that modulate a variety of biological responses, including as hormones, neurotransmitters, and antimicrobials. Occupying the space in between conventional small molecules and biologics, they can also be designed to inhibit large protein-protein interaction surfaces. However, strategies are needed to convert them into more stable molecules while retaining the bioactivity of the native peptides, ideally employing scaffolds that can adopt precise secondary structures while being amenable to rapid derivatization for library synthesis and screening. Towards that goal, we develop new methods for late-stage peptide functionalizations, and devise new strategies for the synthesis and conformational control of acyclic, highly functionalized peptidomimetics. This includes (1) the study of azapeptide folding and the development of new strategies for their chemoselective functionalization and rigidification, and (2) the discovery and application of new conformationally-constrained N-substituted glycine peptoid monomers. These novel methods are then applied to the synthesis of bioactive peptide analogs.

摘要 我们的研究计划集中在开发新的广泛适用的多肽模拟工具。 多肽是一类重要的化合物，可以调节各种生物反应，包括 作为激素、神经递质和抗菌剂。占据常规小空间之间的空间 除了分子和生物制品，它们还可以被设计成抑制大的蛋白质-蛋白质相互作用表面。 然而，需要一些策略来将它们转化为更稳定的分子，同时保持生物活性。 最理想的是使用能够采用精确的二级结构的支架，而 适合于文库合成和筛选的快速衍生化。为了实现这一目标，我们发展 晚期多肽功能化的新方法，并设计新的合成策略和 无环、高度功能化的多肽模拟物的构象控制。这包括(1)研究 氮肽折叠及其化学选择性功能化新策略的研究进展 刚性，以及(2)新构象受限N-取代的发现和应用 甘氨酸类肽类单体。这些新方法被应用于生物活性多肽的合成。 类比。

项目成果

Late-Stage Chloride Displacements Enable Access to Peptoids with cis-Inducing Alkylammonium Side Chains.

后期氯化物置换能够获得具有顺式诱导烷基铵侧链的类肽。

• DOI: 10.1021/acs.orglett.3c02393
• 发表时间: 2023
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Davern,CarolynnM;Proulx,Caroline
• 通讯作者: Proulx,Caroline