Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimics.
O-Carbamoylserine and O-carbamoylthreonine are glutamine analogues that were incorporated into a Stat3 inhibitory peptide to probe the requirements of Gln at the pY+3 position. Fmoc-Ser-NHBn and Fmoc-Thr-NHBn were converted to nitrophenyl carbonates and were attached to Rink resin via a side-chain carbamate linkage. After assembly of the peptide, acid treatment resulted in O-carbamoylserine and O-carbamoylthreonine-containing peptides. The order of affinity for Stat3 was Gln > Ser(CONH2) >> Thr(CONH2) suggesting a relatively tight binding pocket for the side chain of glutamine.
Mandal
Pijus K
PK
The University of Texas, MD Anderson Cancer Center, Department of Experimental Therapeutics, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Heard
Patricia A
PA
Ren
Zhiyong
Z
Chen
Xiaomin
X
McMurray
John S
JS
D018360:Crystallography, X-Ray; D005973:Glutamine / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D012694:Serine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013912:Threonine / Q000031:analogs & derivatives* / Q000737:chemistry; D018909:src Homology Domains / Q000187:drug effects
D007202:Indicators and Reagents; C518523:O-carbamoylthreonine; D050796:STAT3 Transcription Factor; D005973:Glutamine; D013912:Threonine; C000366:O-carbamylserine; D012694:Serine