Yu Limin, Yu Peggy Shuang, Yee Yen Mui Elizabeth, McKelvie Jennifer C, Pham Thi Phuong Tu, Yap Yan Wen, Wong Wan Qing, Wu Jiawen, Deng Weiqiao, Orner Brendan P
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Bioorg Med Chem. 2009 Jul 1;17(13):4825-32. doi: 10.1016/j.bmc.2009.03.054. Epub 2009 Apr 1.
A novel selection approach is presented to screen phage display peptide libraries against sets of receptors that share specificity for the same ligand. This strategy was applied to the discovery of glycomimetic peptides. Through these screens, a number of peptide clones were discovered that bind the lectins used in the screen, in a sugar competitive manner. In addition, the majority of the selected peptides demonstrate sugar type mimicry consistent with lectin specificity. Docking studies were conducted to establish whether the mimetic peptides bind to the lectin ConA at the sugar binding site or to a nearby, alternative site shown to bind to YPY-containing peptides previously discovered from single-target screens. Of the three cyclic peptides subjected to computational docking, CNTPLTSRC had the highest predicted affinity and CSRILTAAC demonstrated specificity for the sugar binding site comparable to the natural ligand itself.
本文提出了一种新颖的筛选方法，用于针对对同一配体具有共同特异性的受体组筛选噬菌体展示肽库。该策略被应用于发现拟糖肽。通过这些筛选，发现了许多以糖竞争方式结合筛选中使用的凝集素的肽克隆。此外，大多数所选肽表现出与凝集素特异性一致的糖型模拟。进行对接研究以确定模拟肽是在糖结合位点与凝集素ConA结合，还是与先前从单靶点筛选中发现的含YPY肽结合的附近替代位点结合。在进行计算对接的三个环肽中，CNTPLTSRC具有最高的预测亲和力，CSRILTAAC对糖结合位点的特异性与天然配体本身相当。
