L
Larry W. Hardy
Researcher at Sunovion
Publications - 40
Citations - 1513
Larry W. Hardy is an academic researcher from Sunovion. The author has contributed to research in topics: Reuptake inhibitor & Reuptake. The author has an hindex of 17, co-authored 39 publications receiving 1430 citations. Previous affiliations of Larry W. Hardy include University of Massachusetts Medical School.
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Journal ArticleDOI
Systematic mutation of bacteriophage T4 lysozyme.
TL;DR: Of the resulting 2015 single amino acid substitutions in T4 lysozyme, 328 were found to be sufficiently deleterious to inhibit plaque formation, and more than half (55%) of the positions in the protein tolerated all substitutions examined.
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The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major.
TL;DR: PTR1 exhibited 2000-fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase-thymidylate synthase, suggesting several mechanisms by which P TR1 may compromise antifolate inhibition in wild-type Leishmania and lines bearing PTR1amplifications.
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PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major.
TL;DR: The concordance of the biochemical and genetic properties of PTR1 suggests that this is the primary enzyme mediating pteridine salvage, and these findings suggest several possible mechanisms for P TR1-mediated MTX resistance and should aid in the design of rational chemotherapy.
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Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites
David G. Gourley,Alexander W. Schüttelkopf,Gordon A. Leonard,James Luba,Larry W. Hardy,Stephen M. Beverley,William N. Hunter +6 more
TL;DR: Crystal structures of PTR1 complexed with cofactor and 7,8-dihydrobiopterin (DHB) or methotrexate (MTX) delineate the enzyme mechanism, broad spectrum of activity and inhibition by substrate or an antifolate.
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New approaches to Leishmania chemotherapy: pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity
TL;DR: Findings suggest that successful antifolate chemotherapy in Leishmania will have to target simultaneously both DHFR and PTR1, which has the potential to act as a by-pass and/or modulator of DHFR inhibition under physiological conditions.