Rapid assembly and in situ screening of bidentate inhibitors of protein tyrosine phosphatases.
[reaction: see text] We have successfully designed and synthesized a small library of protein tyrosine phosphatase (PTP) inhibitors, in which the so-called "click chemistry" or Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction was carried out for rapid assembly of 66 different bidentate compounds. Subsequent in situ enzymatic screening revealed a potential PTP1B inhibitor (IC(50) = 4.7 microM) which is 10-100 fold more potent than other PTPs.
Department of Chemistry, Medicinal Chemistry Program of the Office of Life Sciences, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore.
Rajavel
R
Srinivasan
Mahesh
M
Uttamchandani
Shao Q
SQ
Yao
D001665:Binding Sites / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D007555:Isoxazoles; D014230:Triazoles; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases