New Syntheses of Tetrazolylmethylphenylalanine and O‐Malonyltyrosine as pTyr Mimetics for the Design of STAT3 Dimerization Inhibitors.

Abstract

New syntheses of tetrazolylmethylphenylalanine and O-malonyltyrosine as pTyr mimetics for the design of STAT3 dimerization inhibitors..

Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling

“…Several authors have reported the development of Stat3 inhibitors that incorporate phopshotyrosine or phosphotyrosine mimic 71-76. These compounds did not contain glutamine or a mimic and displayed low affinity for the target, as judged by electrophoretic mobility shift assays or fluorescence polarization.…”

Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3

“…1 H NMR (CDCl 3 , 300 MHz) δ1.31À1.38 (m, 6H), 2.58 (s, 3H), 4.17À4.28 (m, 4H), 7.31 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 8.7 Hz, 2H). 13 C NMR (CDCl 3 , 75.0 MHz) δ 16.0, 26.5, 64.8, 82.5, 119.9, 130.3, 133.9, 154.4, 196.6. HRMS (M þ H) calcd, 273.0892; found, 273.0965.…”

“…1 H NMR (CDCl 3 , 300 MHz) δ1.32À1.37 (m, 6H), 1.51 (s, 9H), 2.50 (s, 3H), 4.16À4.27 (m, 4H), 6.0 (s, 1H), 7.2 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H). 13 Synthesis of Pentachlorophenyl (E)-3-(4-Diethoxyphosphorylphenyl)but-2-enoate, 24. A solution of 23 (2.00 g, 6.4 mmol), pentachlorophenol (1.9 g, 7.0 mmol), DCC (1.6 g, 7.7 mmol), and DMAP (0.08 g, 0.64 mmol) in 100 mL of ethyl acetate was stirred at room temperature for 24 h. The mixture was filtered through Celite and the solvent removed in vacuuo.…”

Molecular Approaches towards the Inhibition of the Signal Transducer and Activator of Transcription 3 (Stat3) Protein

“…[33] Substitution of the phosphate group with an O -methylenecarboxylic acid ( 23b ) or tetrazole ( 23c or 23d ), a more lipophilic bioisostere of a carboxylic acid, was poorly tolerated. It is suggested that mono-anionic pTyr mimetics are incapable of forming as many hydrogen bonds and salt bridges with the two positively charged amino acid residues in the pTyr binding pocket, specifically Lys 591 and Arg 609, compared with pTyr.…”