Tyrosine modified analogues of the ¦Á4¦Â7 integrin inhibitor biotin-R₈ERY prepared via Click Chemistry: Synthesis and biological evaluation

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• 作者：Stefanie Papst^a ; Anaï ; s Noisier^a ; Margaret A. Brimble^a ; ^{m.brimble@auckland.ac.nz} ; Yi Yang^b ; Geoffrey W. Krissansen^b
• 关键词：CuAAC ; copper catalyzed azide-alkyne cycloaddition ; FAK ; focal adhesion kinase ; FBS ; fetal bovine serum ; GALT ; gut-associated lymphoid tissues ; GnHCl ; guanidine hydrochloride ; GVHD ; graft-versus-host disease ; HBSS ; Hank&rsquo ; s buffered salt solution ; HMP
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：15 April, 2012
• 年：2012
• 卷：20
• 期：8
• 页码：2638-2644
• 全文大小：1398 K

文摘

Our continuing programme aiming at developing inhibitors of integrin ¦Á4¦Â7, a key mediator of various inflammatory diseases, led us to synthesise a library of cell-permeable peptides based on the biotin-R₈ERY^{?/sup> 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 Mn2+-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-r₉YDRREY at concentrations of 100 and 50 ¦ÌM, with 14 exhibiting an IC₅₀ of less than 10 ¦ÌM.}