Azide–alkyne cycloaddition affording enzymatically tunable bisubstrate based inhibitors of histone acetyltransferase PCAF

van Ameijde, J., Zwiebel, A. P. R., Ruijtenbeek, R. and Liskamp, R. M. J. (2014) Azide–alkyne cycloaddition affording enzymatically tunable bisubstrate based inhibitors of histone acetyltransferase PCAF. Bioorganic and Medicinal Chemistry Letters, 24(1), pp. 113-116. (doi: 10.1016/j.bmcl.2013.11.060)

Abstract

A novel strategy to prepare bisubstrate based inhibitors for histone acetyltransferases is presented. To obtain these, azido peptides derived from histone H3 incorporating either a serine or a phosphoserine residue were connected to a propargyl coenzyme A derivative through copper catalyzed click chemistry. The resulting inhibitors were tested with therapeutically relevant acetyltransferase PCAF. Increased potency of the phosphoserine containing inhibitor was observed. The synthetic strategy presented may be used for developing bisubstrate based inhibitors against any acetyltransferase.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert
• Authors: van Ameijde, J., Zwiebel, A. P. R., Ruijtenbeek, R., and Liskamp, R. M. J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Bioorganic and Medicinal Chemistry Letters
• Publisher: Elsevier
• ISSN: 0960-894X
• ISSN (Online): 1464-3405