Shroff H N, Schwender C F, Baxter A D, Brookfield F, Payne L J, Cochran N A, Gallant D L, Briskin M J
LeukoSite, Inc., Cambridge, MA 02142, USA.
Bioorg Med Chem Lett. 1998 Jul 7;8(13):1601-6. doi: 10.1016/s0960-894x(98)00286-8.
MAdCAM-1 specifically binds the lymphocyte integrin alpha 4 beta 7 and participates in the homing of leukocytes to intestinal mucosal sites. The LDT sequence located on the CD loop of MAdCAM-1 is an important binding site for MAdCAM-1/alpha 4 beta 7 interactions. N-Terminus acylation of the LDT motif and modification of the C-terminus carboxamide with amines led to low micromolar MAdCAM-1 inhibitors.
黏膜地址素细胞黏附分子-1（MAdCAM-1）特异性结合淋巴细胞整合素α4β7，并参与白细胞归巢至肠道黏膜部位的过程。位于MAdCAM-1的CD环上的LDT序列是MAdCAM-1与α4β7相互作用的重要结合位点。LDT基序的N端酰化以及用胺对C端羧酰胺进行修饰可产生低微摩尔浓度的MAdCAM-1抑制剂。
