190604-21-8Relevant articles and documents
Non-peptide RGD surrogates which mimic a Gly-Asp β-turn: Potent antagonists of platelet glycoprotein IIb-IIIa
Fisher, Matthew J.,Gunn, Bruce,Harms, Cathy S.,Kline, Allen D.,Mullaney, Jeffrey T.,Nunes, Anne,Scarborough, Robert M.,Arfsten, Ann E.,Skelton, Marshall A.,Um, Suzane L.,Utterback, Barbara G.,Jakubowski, Joseph A.
, p. 2085 - 2101 (2007/10/03)
Cyclic heptapeptide 1, which contains an Arg-Gly-Asp sequence, has good affinity for the platelet receptor GPIIb-IIIa and was chosen for study by 1H NMR techniques. The key RGD sequence of this molecule was found to reside in a conformationally defined type II' Gly-Asp β-turn, and this information was used in the design of simple non-peptide RGD mimics. Disubstituted isoquinolones, bearing an acidic side chain at position 2 and a basic side chain at position 6, were prepared and were found to have modest affinity for GPIIb-IIIa. Systematic modification of the basic residue contained in these molecules yielded compounds with high affinity for GPIIb-IIIa.