William C. Lumma
United States Military Academy
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by William C. Lumma.
Bioorganic & Medicinal Chemistry Letters | 1995
Steven D. Young; Muriel C. Amblard; Susan F. Britcher; Vanessa E. Grey; Lee O. Tran; William C. Lumma; Joel R. Huff; William A. Schleif; Emilio E. Emini; Julie A. O'Brien; Douglas J. Pettibone
Abstract A variety of 2-heterocycle substituted 3-phenysulfonyl-5-chloroindoles were investigated as replacements for the 2-carboxamide functionality of the potent HIV-1 reverse transcriptase inhibitor L-737, 126. The 2-carboxamide series of compounds typified by L-737,126 have poor solubility. Replacement of the carboxamide moiety with a variety of heterocycles results in a series of potent enzyme inhibitors with equivalent ex vivo antiviral activity and improved physicochemical properties.
Journal of Biological Chemistry | 2001
Hans E. Huber; Ronald G. Robinson; Aubrey Watkins; Deborah D. Nahas; Marc T. Abrams; Carolyn A. Buser; Robert B. Lobell; Denis R. Patrick; Neville J. Anthony; Christopher J. Dinsmore; Samuel L. Graham; George D. Hartman; William C. Lumma; Theresa M. Williams; D C Heimbrook
We have identified and characterized potent and specific inhibitors of geranylgeranyl-protein transferase type I (GGPTase I), as well as dual inhibitors of GGPTase I and farnesyl-protein transferase. Many of these inhibitors require the presence of phosphate anions for maximum activity against GGPTase Iin vitro. Inhibitors with a strong anion dependence were competitive with geranylgeranyl pyrophosphate (GGPP), rather than with the peptide substrate, which had served as the original template for inhibitor design. One of the most effective anions was ATP, which at low millimolar concentrations increased the potency of GGPTase I inhibitors up to several hundred-fold. In the case of clinical candidate l-778,123, this increase in potency was shown to result from two major interactions: competitive binding of inhibitor and GGPP, and competitive binding of ATP and GGPP. At 5 mm, ATP caused an increase in the apparent K d for the GGPP-GGPTase I interaction from 20 pm to 4 nm, resulting in correspondingly tighter inhibitor binding. A subset of very potent GGPP-competitive inhibitors displayed slow tight binding to GGPTase I with apparent on and off rates on the order of 106 m − 1s− 1 and 10− 3s− 1, respectively. Slow binding and the anion requirement suggest that these inhibitors may act as transition state analogs. After accounting for anion requirement, slow binding, and mechanism of competition, the structure-activity relationship determined in vitro correlated well with the inhibition of processing of GGPTase I substrate Rap1a in vivo.
Bioorganic & Medicinal Chemistry Letters | 2002
Thomas J. Tucker; Marc T. Abrams; Carolyn A. Buser; Joseph P. Davide; Michelle Ellis-Hutchings; Christine Fernandes; Jackson B. Gibbs; Samuel L. Graham; George D. Hartman; Hans E. Huber; Dongming Liu; Robert B. Lobell; William C. Lumma; Ronald G. Robinson; John T. Sisko; Smith Am
We have prepared a series of potent, dual inhibitors of the prenyl transferases farnesyl protein transferase (FPTase) and geranyl-geranyl protein transferase I (GGPTase). The compounds were shown to possess potent activity against both enzymes in cell culture. Mechanistic analysis has shown that the compounds are CAAX competitive for FPTase inhibition but geranyl-geranyl pyrophosphate (GGPP) competitive for GGPTase inhibiton.
Bioorganic & Medicinal Chemistry Letters | 2001
B. Wesley Trotter; Amy G. Quigley; William C. Lumma; John T. Sisko; Eileen S. Walsh; Christian S. Hamann; Ronald G. Robinson; Hema Bhimnathwala; D. Garrett Kolodin; Wei Zheng; Carolyn A. Buser; Hans E. Huber; Robert B. Lobell; Nancy E. Kohl; Theresa M. Williams; Samuel L. Graham; Christopher J. Dinsmore
A series of 2-arylindole-3-acetamide farnesyl protein transferase inhibitors has been identified. The compounds inhibit the enzyme in a farnesyl pyrophosphate-competitive manner and are selective for farnesyl protein transferase over the related enzyme geranylgeranyltransferase-I. A representative member of this series of inhibitors demonstrates equal effectiveness against HDJ-2 and K-Ras farnesylation in a cell-based assay when geranylgeranylation is suppressed.
Cancer Research | 2001
Robert B. Lobell; Charles Omer; Marc Abrams; Hema Bhimnathwala; Mary Jo Brucker; Carolyn A. Buser; Joseph P. Davide; S. Jane Desolms; Christopher J. Dinsmore; Michelle Ellis-Hutchings; Astrid M. Kral; Dongming Liu; William C. Lumma; Samuel V. Machotka; Elaine Rands; Theresa M. Williams; Samuel Graham; George D. Hartman; Allen Oliff; David C. Heimbrook; Nancy E. Kohl
Journal of the American Chemical Society | 1995
Keith M. Witherup; Richard W. Ransom; Amy C. Graham; Aurora M. Bernard; Michael J. Salvatore; William C. Lumma; Paul S. Anderson; Steven M. Pitzenberger; Sandor L. Varga
Journal of Medicinal Chemistry | 1998
William C. Lumma; Witherup Km; Thomas J. Tucker; Stephen F. Brady; John T. Sisko; Adel M. Naylor-Olsen; Lewis Sd; Bobby J. Lucas; Joseph P. Vacca
Journal of Medicinal Chemistry | 1994
Thomas J. Tucker; Terry A. Lyle; Catherine M. Wiscount; Susan F. Britcher; Steven D. Young; William M. Sanders; William C. Lumma; Mark E. Goldman; Julie A. O'Brien
Journal of Medicinal Chemistry | 1983
Jacob M. Hoffman; Adolph M. Pietruszkiewicz; Charles N. Habecker; Brian T. Phillips; William A. Bolhofer; Edward J. Cragoe; Mary Lou Torchiana; William C. Lumma; John J. Baldwin
Journal of Medicinal Chemistry | 1982
William C. Lumma; Anderson Ps; John J. Baldwin; William A. Bolhofer; Charles N. Habecker; Hirshfield Jm; Pietruszkiewicz Am; Randall Wc; Mary Lou Torchiana; Britcher Sf; Clineschmidt Bv; Denny Gh; Ralph Hirschmann; Hoffman Mj; Brian T. Phillips; Streeter Kb