Abstract
Geldanamycin, streptoval C, streptovarone, and dapmavarone preferentially inhibited terminal deoxynucleotidyltransferase activity of Molt-4 cells and leukocytes from an acute lymphoblastic leukemia patient as compared with DNA polymerase α, β, and γ activities of these cells or of phytohemagglutinin-stimulated normal human lymphocytes. Streptovaricin C, the parent compound from which streptoval C, streptovarone, and dapmavarone are derived, was a poor inhibitor of these enzyme activities. Geldanamycin, streptoval C, and streptovarone inhibited terminal deoxynucleotidyltransferase activity more than reverse transcriptase activity of simian sarcoma virus, but dapmavarone inhibited these enzyme activities about the same. Inhibition of terminal deoxynucleotidyltransferase activity by these compounds was reversed by dilution but not by addition of extra initiator [(dA)12-18], a divalent cation (Mn2+), bovine serum albumin, or substrate (dGTP). Prior incubation of each compound with the transferase resulted in greater inhibition than prior incubation with initiator or lack of prior incubation. These findings suggest that geldanamycin, streptoval C, streptovarone, and dapmavarone preferentially inhibit terminal deoxynucleotidyltransferase activity by reversibly binding to the enzyme and not to initiator or divalent cation.
- Copyright © 1978 by Academic Press, Inc.
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