title: Tyrosine modified analogues of the α4β7 integrin inhibitor biotin-R₈ERY prepared via Click Chemistry: synthesis and biological evaluation.
abstract: Our continuing programme aiming at developing inhibitors of integrin α4β7, a key mediator of various inflammatory diseases, led us to synthesise a library of cell-permeable peptides based on the biotin-R(8)ERY(∗) template, wherein the tyrosine residue has been modified by using the CuAAC reaction. The peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit Mn(2+)-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. Two of the synthesised peptidomimetics, analogues 11 and 14, are more active than our previously reported lead compound biotin-r(9)YDRREY at concentrations of 100 and 50 μM, with 14 exhibiting an IC(50) of less than 10 μM.
authors.affiliation: School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland Central 1010, New Zealand.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Papst
authors.forename: Anaïs
authors.initials: A
authors.lastname: Noisier
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Brimble
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Krissansen
mesh_terms: D000818:Animals; D001710:Biotin / Q000737:chemistry*; D002460:Cell Line; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D016023:Integrins / Q000037:antagonists & inhibitors*; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D016023:Integrins; D009842:Oligopeptides; C071777:integrin alpha4beta7; D014443:Tyrosine; D001710:Biotin