title: Synthesis of phosphatase-stable, cell-permeable peptidomimetic prodrugs that target the SH2 domain of Stat3.
abstract: 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.
authors: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors: Pijus K
authors: PK
authors: Mandal
authors: Warren S-L
authors: WS
authors: Liao
authors: John S
authors: JS
authors: McMurray
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; C544848:BP-PM279G; C544847:BP-PM6; D006575:Heterocyclic Compounds, 3-Ring; D011355:Prodrugs; D011759:Pyrrolidines; D050796:STAT3 Transcription Factor; D019000:Phosphotyrosine