Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors
Adéla Jílková, Petra Rubešová, Jindřich Fanfrlík, Pavla Fajtová, Pavlína Řezáčová, J. Brynda, Martin Lepšı́k, Helena Mertlíková‐Kaiserová, Cory D. Emal, Adam R. Renslo, William Roush, Martin Horn, Conor R. Caffrey, Michael A. Mares
Abstract
-hydroxysulfonic amide moiety and displays favorable functional properties, including bioactivity against the pathogen, selectivity for SmCB1 over human cathepsin B, and reasonable metabolic stability. Our results provide structural insights for the rational design of next-generation SmCB1 inhibitors as potential drugs to treat schistosomiasis.
Topics & Concepts
DruggabilityPeptidomimeticCathepsin BVirtual screeningSulfoneChemistryDrug discoveryCathepsin DBiologyPhage displayBiochemistryStereochemistryEnzymePeptideGenePolymer chemistryParasites and Host InteractionsResearch on Leishmaniasis StudiesMalaria Research and Control