1203698-11-6Relevant articles and documents
4-Aminoproline-based arginine-glycine-aspartate integrin binders with exposed ligation points: Practical in-solution synthesis, conjugation and binding affinity evaluation
Battistini, Lucia,Burreddu, Paola,Carta, Paola,Rassu, Gloria,Auzzas, Luciana,Curti, Claudio,Zanardi, Franca,Manzoni, Leonardo,Araldi, Elena M. V.,Scolastico, Carlo,Casiraghi, Giovanni
experimental part, p. 4924 - 4935 (2010/02/15)
An expedient and practical in-solution synthesis of three new 4-aminoproline-based arginine-glycine-aspartate integrin binders - compounds 15, 17 and 19- is presented. Two candidates carrying exposed azide and amine functional points were further advanced to trimeric platform 21 as well as fluorescein- and DOTA-conjugates 23 and 25. The new compounds were assayed for their binding affinity towards human αVβ3 and αVβ5 integrin receptors. Both monomeric candidates and covalent conjugates revealed potent ligand competence for the αVβ3 receptor in the one-digit nanomolar range (IC50αVβ3 = 0.2-8.0 nM; IC 50αVβ5 = 5.0-1621 nM), thus demonstrating that conjugation does not impair the exquisite binding profile of this new generation of integrin ligands. The Royal Society of Chemistry 2009.