title: Phage display screening against a set of targets to establish peptide-based sugar mimetics and molecular docking to predict binding site.
abstract: 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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors.forename: Limin
authors.initials: L
authors.lastname: Yu
authors.forename: Peggy Shuang
authors.initials: PS
authors.lastname: Yu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yee Yen Mui
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: McKelvie
authors.forename: Thi Phuong Tu
authors.initials: TP
authors.lastname: Pham
authors.forename: Yan Wen
authors.initials: YW
authors.lastname: Yap
authors.forename: Wan Qing
authors.initials: WQ
authors.lastname: Wong
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wu
authors.forename: Weiqiao
authors.initials: W
authors.lastname: Deng
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Orner
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D032701:Biomimetics; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry*; D003198:Computer Simulation; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002241:Carbohydrates; D037102:Lectins; D008024:Ligands; D019151:Peptide Library; D010455:Peptides