New syntheses of tetrazolylmethylphenylalanine and O-malonyltyrosine as pTyr mimetics for the design of STAT3 dimerization inhibitors.
Investigation within the pTyr-binding pocket of the STAT3 SH2 domain led us to develop a novel synthesis of two pTyr mimetics, l-tetrazolylmethylphenylalanine (l-Tmp) and l-O-malonyltyrosine (l-OMT), that were next incorporated in a high affinity ligand of STAT3 SH2 domain. Biological evaluation of peptidomimetics on STAT3 dimerization identified l-OMT as the first non-phosphorus pTyr mimetic so far reported against STAT3 SH2 domain, harboring an activity similar to that of the Pmp-containing reference peptidomimetic.
Dourlat
Jennifer
J
Université Paris Descartes, UFR Biomédicale, Laboratoire de Pharmacochimie Moléculaire et Cellulaire, Paris F-75006, France.
Valentin
Bruno
B
Liu
Wang-Qing
WQ
Garbay
Christiane
C
D019281:Dimerization; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D018716:Molecular Mimicry; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D050796:STAT3 Transcription Factor; D014443:Tyrosine; D010649:Phenylalanine