Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site: structural variants of the C-terminal Phe

Gail E Atkinson; Angela Cowan; Campbell McInnes; Daniella I Zheleva; Peter M Fischer; Weng C Chan

doi:10.1016/s0960-894x(02)00508-5

Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site: structural variants of the C-terminal Phe

Bioorg Med Chem Lett. 2002 Sep 16;12(18):2501-5. doi: 10.1016/s0960-894x(02)00508-5.

Authors

Gail E Atkinson¹, Angela Cowan, Campbell McInnes, Daniella I Zheleva, Peter M Fischer, Weng C Chan

Affiliation

¹ School of Pharmaceutical Sciences, University of Nottingham, University Park, NG7 2RD, Nottingham, UK.

PMID: 12182847
DOI: 10.1016/s0960-894x(02)00508-5

Abstract

A focused series of octapeptides based on the lead compound H-His-Ala-Lys-Arg-Arg-Leu-Ile-Phe-NH(2) 1, in which the C-terminal phenylalanine residue was replaced by alpha and/or beta-modified variants, was synthesized using solid-phase chemistry. Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. Unexpectedly, the D-threo-Pse derivatives also showed inhibitory activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
CDC2-CDC28 Kinases*
Chromatography, High Pressure Liquid
Cyclin A / antagonists & inhibitors*
Cyclin A / chemistry
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / antagonists & inhibitors*
Cyclin-Dependent Kinases / chemistry
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Models, Molecular
Peptides / chemistry
Peptides / pharmacology*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / chemistry

Substances

Cyclin A
Enzyme Inhibitors
Peptides
Protein Serine-Threonine Kinases
CDC2-CDC28 Kinases
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases