444899-84-7Relevant academic research and scientific papers
Novel μ opioid antagonists derived from the μ opioid agonists endomorphin and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2)
Shi, Saijian,Xu, Jian,Feng, LingLing,Fan, Xin,Chen, Zhen,Qin, Yajuan,Chung, Nga N.,Li, Tingyou,Schiller, Peter W.
, p. 1305 - 1314 (2020/08/05)
Hybrid analogues of the μ opioid agonists endomorphin and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2, Dmt?=?2′,6′-dimethyltyrosine) containing cis-4-amino-Pro, trans-4-amino-Pro, cis-4-aminoethyl-Pro or cis-4-guanidinylethyl-Pro in the 2 p
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
supporting information; 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.
Discovery of subnanomolar arginine-glycine-aspartate-based αvβ3/αvβ5 integrin binders embedding 4-aminoproline residues
Zanardi, Franca,Burreddu, Paola,Rassu, Gloria,Auzzas, Luciana,Battistini, Lucia,Curti, Claudio,Sartori, Andrea,Nicastro, Giuseppe,Menchi, Gloria,Cini, Nicoletta,Bottonocetti, Anna,Raspanti, Silvia,Casiraghi, Giovanni
, p. 1771 - 1782 (2008/09/21)
The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity αvβ3/αvβ 5 integrin binders [IC50h(αvβ 3) 0.03-5.12 nM; IC50h(αvβ 5) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the Nα- nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the αvβ3 receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin αvβ3 complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.
