Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4019-22. doi: 10.1016/j.bmcl.2014.06.016. Epub 2014 Jun 16.

Inhibition of the lymphoid tyrosine phosphatase: the effect of zinc(II) ions and chelating ligand fragments on enzymatic activity.

Author information

1
Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
2
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA. Electronic address: Amy.Barrios@Utah.edu.

Abstract

A 96-member chelator fragment library (CFL-1.1) was screened to identify inhibitors of the lymphoid tyrosine phosphatase in the absence and presence of zinc acetate. Fragments that inhibit LYP activity more potently in the presence of zinc, fragments that rescue LYP activity in the presence of inhibitory concentrations of zinc, and fragments that inhibit LYP activity independent of zinc concentration were identified. Of these, 1,2-dihydroxynaphthalene was the most potent inhibitor with an IC50 value of 2.52±0.06 μM after 2 h of incubation. LYP inhibition by 1,2-dihydroxynaphthalene was very similar to inhibition by 1,2-naphthoquinone (IC50=1.10±0.03 µM), indicating that the oxidized quinone species is likely the active inhibitor. The inhibition was time-dependent, consistent with covalent modification of the enzyme.

KEYWORDS:

Chelator fragment library; Enzyme inhibitors; Protein tyrosine phosphatase

PMID:
24997687
PMCID:
PMC4497560
DOI:
10.1016/j.bmcl.2014.06.016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center