Pulchellalactam: A CD45 Protein Tyrosine Phosphatase Inhibitor from the Marine Fungus Corollospora pulchella.

The Journal of Antibiotics
1998.0

Abstract

As a part of our effort to find enzyme inhibitors from microbial sources, we identified a fungal extract of Corollospora pulchella which exhibited very potent activity in our CD45 assay. Bioassay directed fractionation of the crude extract yielded a novel pulchellalactam (1) as the active component. Here we describe the isolation, structure determination and biological characteristics of 1. Pulchellalactam was isolated as an oily material with the molecular formula C9H13NO determined by HREI-MS analysis. Its structure was established by NMR spectroscopy (1H, 13C, DEPT, HMQC, COSY, HMBC). Pulchellalactam exhibited a dose-dependent inhibition of CD45 activity with an IC50 of 124μg/ml, comparable to the known tyrosine phosphatase inhibitor sodium orthovanadate which inhibited CD45 activity with an IC50 of 91.9μg/ml. The inhibition was specific for CD45 as another protein tyrosine phosphatase, PTP 1B, was not inhibited by pulchellalactam.

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