title: Synthesis and in Vitro Evaluation of a Peptidomimetic Inhibitor Targeting the Src Homology 2 (SH2) Domain of STAT6.
abstract: An improved synthesis of a phosphopeptidomimetic prodrug targeting the Src Homology 2 (SH2) domain of signal transducer and activator of transcription 6 (STAT6) is reported. In our convergent methodology, we employed a phosphotyrosine surrogate active ester harboring pivaloyloxymethyl groups, which efficiently coupled to tert-butylglycinyl proline diarylamide. Biological evaluation of 1 has not been reported. We show that it inhibits STAT6 phosphorylation in intact human bronchial epithelial cells, suggesting potential application in the treatment of asthma.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center , 1901 East Road, Houston, Texas 77054, United States.
authors.forename: Pietro
authors.initials: P
authors.lastname: Morlacchi
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center , 1901 East Road, Houston, Texas 77054, United States.
authors.forename: Pijus K
authors.initials: PK
authors.lastname: Mandal
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center , 1901 East Road, Houston, Texas 77054, United States.
authors.forename: John S
authors.initials: JS
authors.lastname: McMurray
keywords: Peptidomimetic inhibitor; SH2; STAT6; prodrug