Affinity-Enhanced Luminescent Re(I)- and Ru(II)-Based Inhibitors of the Cysteine Protease Cathepsin L.

ABSTRACT: Two new Re(I)- and Ru(II)-based inhibitors were synthesized with the formulas [Re(phen)(CO)₃(1)](OTf) (7; phen = 1,10-phenanthroline, OTf = trifluoromethanesulfonate) and [Ru(bpy)₂(2)](Cl)₂ (8; bpy = 2,2'-bipyridine), where 1 and 2 are the analogues of CLIK-148, an epoxysuccinyl-based cysteine cathepsin L inhibitor (CTSL). Compounds 7 and 8 were characterized using various spectroscopic techniques and elemental analysis; 7 and 8 both show exceptionally long excited state lifetimes. Re(I)-based complex 7 inhibits CTSL in the low nanomolar range, affording a greater than 16-fold enhancement of potency relative to the free inhibitor 1 with a second-order rate constant of 211000 ± 42000 M^-1 s^-1. Irreversible ligation of 7 to papain, a mode

SUBMITTER: Huisman M 

PROVIDER: S-EPMC6034508 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature