Identification of a high-affinity phosphopeptide inhibitor of Stat3

Zhiyong Ren; Larry A Cabell; Timothy S Schaefer; John S McMurray

doi:10.1016/s0960-894x(02)01050-8

Identification of a high-affinity phosphopeptide inhibitor of Stat3

Bioorg Med Chem Lett. 2003 Feb 24;13(4):633-6. doi: 10.1016/s0960-894x(02)01050-8.

Authors

Zhiyong Ren¹, Larry A Cabell, Timothy S Schaefer, John S McMurray

Affiliation

¹ Department of Neuro-Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

PMID: 12639546
DOI: 10.1016/s0960-894x(02)01050-8

Abstract

Stat3 is a latent transcription factor that exhibits elevated activity in a variety of human cancers. To find a lead peptide for peptidomimetic drug development we synthesized and tested phosphopeptides derived from known receptor docking sites and found Y(p)LPQTV as the optimal sequence. SAR studies showed that each residue from pY to pY+3 provided binding energy.

Publication types

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

MeSH terms

Amino Acid Sequence
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology
DNA / metabolism
DNA-Binding Proteins / antagonists & inhibitors*
Dimerization
Humans
Inhibitory Concentration 50
Phosphopeptides / chemical synthesis
Phosphopeptides / pharmacology*
Protein Binding / drug effects
STAT3 Transcription Factor
Structure-Activity Relationship
Trans-Activators / antagonists & inhibitors*
Transcription Factors / antagonists & inhibitors
src Homology Domains

Substances

Antineoplastic Agents
DNA-Binding Proteins
Phosphopeptides
STAT3 Transcription Factor
STAT3 protein, human
Trans-Activators
Transcription Factors
acetyl-phosphotyrosyl-leucyl-prolyl-glutaminyl-threonyl-valinamide
DNA