Novel modified tripeptide inhibitors of alpha 4 beta 7 mediated lymphoid cell adhesion to MAdCAM-1.
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.
Shroff
H N
HN
LeukoSite, Inc., Cambridge, MA 02142, USA.
Schwender
C F
CF
Baxter
A D
AD
Brookfield
F
F
Payne
L J
LJ
Cochran
N A
NA
Gallant
D L
DL
Briskin
M J
MJ
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D009088:Mucoproteins / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D009842:Oligopeptides; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7