Synthesis of N-Hydroxy Isopeptide Containing Proteins

Org Lett. 2015 Jul 17;17(14):3438-41. doi: 10.1021/acs.orglett.5b01443. Epub 2015 Jun 25.

Abstract

Chemical synthesis of a peptide-ubiquitin conjugate linked by an N-hydroxy isopeptide bond to determine what effect the N-hydroxy group has on the enzymatic hydrolysis of the isopeptide linkage by deubiquitinases is reported. This conjugate was subjected to proteolysis by UCH-L3 in the presence and absence of various metal ions, and no substantive difference in hydrolysis was seen compared to a control lacking the N-hydroxy group. The accessibility of N-hydroxy ubiquitinated substrates may find uses to study other deubiquitinases in particular those which use a zinc ion as a part of their catalytic mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Hydrolysis
  • Models, Molecular
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Proteins / chemical synthesis*
  • Proteins / chemistry
  • Substrate Specificity
  • Ubiquitin-Specific Proteases / chemistry*
  • Ubiquitins / chemical synthesis*
  • Ubiquitins / chemistry
  • Zinc / chemistry

Substances

  • Peptides
  • Proteins
  • Ubiquitins
  • Ubiquitin-Specific Proteases
  • Zinc