PROBING RECEPTOR BOUND CONFORMATIONS BY CYCLIC PEPTIDES

提出了一种组合方法作为阐明 肽配体的受体结合构象。库 引入双脲的模板约束的环肽将 合成了 这些环肽将用于呈现相同的 不同构象的识别元件。 图书馆将 筛选与RGD结合整联蛋白的高亲和力结合 （α 5 β 1、α IIb β 3和α V β 3）。 后续结构 对高结合亲和力肽模拟物的分析将使 说明整合素结合的构象，这是有用的 开发相关治疗药物。 这种一般方法 涉及模板约束的环肽文库的方法可以 适用于任何具有短肽基配体的受体。

A combinatorial approach is proposed as a general method for elucidating the receptor-bound conformation of peptide ligands. A library of template-constrained cyclic peptides incorporating bis-ureas will be synthesized. These cyclic peptides will serve to present the same recognition elements in different conformations. The library will be screened for high affinity binding to the RGD-binding integrins (alpha5beta1, alphaIIbbeta3, and alphaVbeta3). Subsequent structural analysis of the high binding affinity peptidomimetics will enable the elucidation of the integrin-bound conformations which are useful for the development of relevant therapeutic drugs. This general approach involving libraries of template-constrained cyclic peptides can be applied to any receptor with a short peptidyl ligand.