Identification of a high-affinity phosphopeptide inhibitor of Stat3.
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.
Ren
Zhiyong
Z
Department of Neuro-Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Cabell
Larry A
LA
Schaefer
Timothy S
TS
McMurray
John S
JS
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D019281:Dimerization; D006801:Humans; D020128:Inhibitory Concentration 50; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D050796:STAT3 Transcription Factor; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D018909:src Homology Domains
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D010748:Phosphopeptides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C540339:acetyl-phosphotyrosyl-leucyl-prolyl-glutaminyl-threonyl-valinamide; D004247:DNA