Aziridide‐Based Inhibitors of Cathepsin L: Synthesis, Inhibition Activity, and Docking Studies

doi:10.1002/cmdc.200600106

Paper

Aziridide‐Based Inhibitors of Cathepsin L: Synthesis, Inhibition Activity, and Docking Studies

Published Oct 13, 2006 · R. Vičík, M. Busemann, C. Gelhaus

ChemMedChem

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Abstract

A comprehensive screening of N‐acylated aziridine (aziridide) based cysteine protease inhibitors containing either Boc‐Leu‐Caa (Caa=cyclic amino acid), Boc‐Gly‐Caa, or Boc‐Phe‐Ala attached to the aziridine nitrogen atom revealed Boc‐(S)‐Leu‐(S)‐Azy‐(S,S)‐Azi(OBn)2 (18 a) as a highly potent cathepsin L (CL) inhibitor (Ki=13 nM) (Azy=aziridine‐2‐carboxylate, Azi=aziridine‐2,3‐dicarboxylate). Docking studies, which also accounted for the unusual bonding situations (the flexibility and hybridization of the aziridides) predict that the inhibitor adopts a Y shape and spans across the entire active site cleft, binding into both the nonprimed and primed sites of CL.

Study Snapshot

Boc-(S)-Leu-(S)-Azy-(S,S)-Azi(OBn)2 (18 a) is a highly potent cathepsin L inhibitor with a Y shape and binding across the entire active site cleft.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Aziridide‐Based Inhibitors of Cathepsin L: Synthesis, Inhibition Activity, and Docking Studies

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