Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides.
[structure: see text]. A small library of cyclic RGD pseudopentapeptides incorporating stereoisomeric 6,5- and 7,5-fused bicyclic lactams was synthesized with the aim of developing active and selective integrin antagonists. The solid-phase synthesis and activity of these RGD derivatives is described. The approach led to two of the most active known inhibitors of alpha(V)beta3 receptor.
Belvisi
L
L
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, via Venezian 21, I-20133 Milano, Italy.
Bernardi
A
A
Checchia
A
A
Manzoni
L
L
Potenza
D
D
Scolastico
C
C
Castorina
M
M
Cupelli
A
A
Giannini
G
G
Carminati
P
P
Pisano
C
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D003500:Cyclization; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D017433:Protein Structure, Secondary; D011869:Radioligand Assay; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds; D036341:Intercellular Signaling Peptides and Proteins; D007769:Lactams; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019030:Receptors, Vitronectin; C057986:echistatin; C047981:arginyl-glycyl-aspartic acid