Dinghupeptins A-D, Chymotrypsin Inhibitory Cyclodepsipeptides Produced by a Soil-Derived Streptomyces

J Nat Prod. 2018 Sep 28;81(9):1928-1936. doi: 10.1021/acs.jnatprod.7b01009. Epub 2018 Sep 17.

Abstract

Four new cyclodepsipeptides, dinghupeptins A-D (1-4), possessing a rare N5-(2-hydroxylethyl)glutamine moiety, were isolated from cultures of the soil-derived Streptomyces sp. SC0581. Their structures were elucidated by spectroscopic and advanced Marfey's amino acid analysis, and their 3D structures were established by theoretical conformational analysis. Compounds 1 and 2, containing a 3-amino-6-hydroxypiperidone unit, displayed selective inhibition of chymotrypsin with IC50 values of 2.1 and 1.1 μM, respectively. Enzyme kinetic analysis and molecular docking experiments revealed they are competitive inhibitors binding to the active site of chymotrypsin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chymotrypsin / antagonists & inhibitors*
  • Chymotrypsin / chemistry
  • Depsipeptides / chemistry
  • Depsipeptides / isolation & purification*
  • Depsipeptides / pharmacology
  • Humans
  • Kinetics
  • Molecular Docking Simulation
  • Soil Microbiology*
  • Streptomyces / metabolism*

Substances

  • Depsipeptides
  • Chymotrypsin