Synthesis of phosphatase-stable, cell-permeable peptidomimetic prodrugs that target the SH2 domain of Stat3.
The synthesis of prodrugs targeted to the SH2 domain of Stat3 is reported. Using a convergent strategy, the pivaloyloxymethyl phosphonodiester of pentachlorophenyl 4-phosphonodifluoromethylcinnamate, a phosphotyrosine surrogate, was synthesized and used to acylate peptidomimetic fragments that were prepared on solid supports. Two prodrugs described here inhibited the phosphorylation of Stat3 in breast tumor cells.
Mandal
Pijus K
PK
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Liao
Warren S-L
WS
McMurray
John S
JS
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D019281:Dimerization; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000138:chemical synthesis / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D018909:src Homology Domains / Q000187:drug effects*
D000970:Antineoplastic Agents; C544848:BP-PM279G; C544847:BP-PM6; D006575:Heterocyclic Compounds, 3-Ring; D011355:Prodrugs; D011759:Pyrrolidines; D050796:STAT3 Transcription Factor; D019000:Phosphotyrosine