Search Results - "Darke, P. L"

L-735,524: An Orally Bioavailable Human Immunodeficiency Virus Type 1 Protease Inhibitor by Vacca, J. P., Dorsey, B. D., Schleif, W. A., Levin, R. B., McDaniel, S. L., Darke, P. L., Zugay, J., Quintero, J. C., Blahy, O. M., Roth, E., Sardana, V. V., Schlabach, A. J., Graham, P. I., Condra, J. H., Gotlib, L., Holloway, M. K., Lin, J., I.-W. Chen, Vastag, K., Ostovic, D., Anderson, P. S., Emini, E. A., Huff, J. R.

“…To date, numerous inhibitors of the human immunodeficiency virus type 1 protease have been reported, but few have been studied extensively in humans, primarily…”
Get full text

The Herpesvirus Proteases as Targets for Antiviral Chemotherapy by Waxman, Lloyd, Darke, Paul L

“…Viruses of the family Herpesviridae are responsible for a diverse set of human diseases. The available treatments are largely ineffective, with the exception…”
Get full text

L-735,524 : the design of a potent and orally bioavailable HIV protease inhibitor by DORSEY, B. D, LEVIN, R. B, LIN, J. H, CHEN, I.-W, HOLLOWAY, M. K, FITZGERALD, P. M. D, AXEL, M. G, OSTOVIC, D, ANDERSON, P. S, HUFF, J. R, MCDANIEL, S. L, VACCA, J. P, GUARE, J. P, DARKE, P. L, ZUGAY, J. A, EMINI, E. A, SCHLEIF, W. A, QUINTERO, J. C

“…A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into…”
Get full text

An Orally Bioavailable Pyrrolinone Inhibitor of HIV-1 Protease:  Computational Analysis and X-ray Crystal Structure of the Enzyme Complex by Smith, Amos B, Hirschmann, Ralph, Pasternak, Alexander, Yao, Wenquing, Sprengeler, Paul A, Holloway, M. Katharine, Kuo, Lawrence C, Chen, Zhongguo, Darke, Paul L, Schleif, William A

“…We have described several potent inhibitors of the HIV-1 protease, based on the novel 3,5-linked bispyrrolinone scaffold which we developed to mimic the…”
Get full text

Crystallographic analysis of a complex between human immunodeficiency virus type 1 protease and acetyl-pepstatin at 2.0-A resolution by FITZGERALD, P. M. D, MCKEEVER, B. M, VANMIDDLESWORTH, J. F, SPRINGER, J. P, HEIMBACH, J. C, CHIH-TAI LEU, HERBER, W. K, DIXON, R. A. F, DARKE, P. L

“…The mode of binding of acetyl-pepstatin to the protease from the human immunodeficiency virus type 1 (HIV-1) has been determined by x-ray diffraction analysis…”
Get full text

HIV-1 protease specificity of peptide cleavage is sufficient for processing of gag and pol polyproteins by Darke, P L, Nutt, R F, Brady, S F, Garsky, V M, Ciccarone, T M, Leu, C T, Lumma, P K, Freidinger, R M, Veber, D F, Sigal, I S

“…The mature proteins of retroviruses originate as a result of proteolytic cleavages of polyprotein precursors. Retroviruses encode proteases responsible for…”
Get more information

Human immunodeficiency virus protease. Bacterial expression and characterization of the purified aspartic protease by Darke, P L, Leu, C T, Davis, L J, Heimbach, J C, Diehl, R E, Hill, W S, Dixon, R A, Sigal, I S

“…The protease of human immunodeficiency virus has been expressed in Escherichia coli and purified to apparent homogeneity. Immunoreactivity toward anti-protease…”
Get full text

Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors by Dorsey, Bruce D, McDonough, Colleen, McDaniel, Stacey L, Levin, Rhonda B, Newton, Christina L, Hoffman, Jacob M, Darke, Paul L, Zugay-Murphy, Joan A, Emini, Emilio A, Schleif, William A, Olsen, David B, Stahlhut, Mark W, Rutkowski, Carrie A, Kuo, Lawrence C, Lin, Jiunn H, Chen, I-W, Michelson, Stuart R, Holloway, M. Katharine, Huff, Joel R, Vacca, Joseph P

“…Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome…”
Get full text

Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl substituents : X-ray crystal structure assisted design by THOMPSON, W. J, FITZGERALD, P. M. D, SCHWERING, J. E, HOMMICK, C. F, NUNBERG, J, SPRINGER, J. P, HUFF, J. R, HOLLOWAY, M. K, EMINI, E. A, DARKE, P. L, MCKEEVER, B. M, SCHLEIF, W. A, QUINTERO, J. C, ZUGAY, J. A, TUCKER, T. J

“…By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV…”
Get full text

Activity and dimerization of human immunodeficiency virus protease as a function of solvent composition and enzyme concentration by JORDAN, S. P, ZUGAY, J, DARKE, P. L, KUO, L. C

“…The activity of human immunodeficiency virus 1 (HIV-1) protease has been examined as a function of solvent composition, incubation time, and enzyme…”
Get full text

L-687,908, a potent hydroxyethylene containing HIV protease inhibitor by Vacca, Joseph P, Guare, J. P, DeSolms, S. J, Sanders, W. M, Giuliani, E. A, Young, S. D, Darke, P. L, Sigal, I. S, Schleif, W. A

Get full text

Design and synthesis of peptidomimetic inhibitors of HIV-1 protease and renin. Evidence for improved transport by Smith, Amos B, Hirschmann, Ralph, Pasternak, Alexander, Akaishi, Ryouichi, Guzman, Mark C, Jones, David R, Keenan, Terence P, Sprengeler, Paul A, Darke, Paul L

Get full text

Chemical Synthesis and Enzymatic Activity of a 99-Residue Peptide with a Sequence Proposed for the Human Immunodeficiency Virus Protease by Nutt, Ruth F., Brady, Stephen F., Darke, Paul L., Ciccarone, Terrence M., Colton, C. Dylion, Nutt, Elka M., Rodkey, John A., Bennett, Carl D., Waxman, Lloyd H., Sigal, Irving S., Anderson, Paul S., Veber, Daniel F.

“…Retroviral proteins, including those from the human immunodeficiency virus (HIV), are synthesized as polyprotein precursors that require proteolytic cleavage…”
Get full text

Characterization of an active single polypeptide form of the human immunodeficiency virus type 1 protease by DiIanni, C L, Davis, L J, Holloway, M K, Herber, W K, Darke, P L, Kohl, N E, Dixon, R A

“…The pepsin-like aspartyl proteases consist of a single polypeptide chain with topologically similar amino- and carboxyl-terminal domains, each of which…”
Get full text

Purification of active herpes simplex virus-1 protease expressed in Escherichia coli by DARKE, P. L, CHEN, E, HALL, D. L, SARDANA, M. K, VELOSKI, C. A, LAFEMINA, R. L, SHAFER, J. A, KUO, L. C

“…Assembly of viral capsids for replication of herpes simplex virus requires the proteolytic processing of the assembly protein ICP35. The protease responsible…”
Get full text

Dissociation and association of the HIV-1 protease dimer subunits: Equilibria and rates by Darke, Paul L, Hall, Dawn L, Jordan, Susan P, Zugay, Joan A, Shafer, Jules A, Kuo, Lawrence C

“…The kinetics and equilibrium properties were investigated for the interconversion between the active dimer of human immunodeficiency virus 1 (HIV-1) protease…”
Get full text

3-Tetrahydrofuran and pyran urethanes as high-affinity P2-ligands for HIV-1 protease inhibitors by Ghosh, Arun K, Thompson, Wayne J, McKee, Sean P, Duong, Tien T, Lyle, Terry A, Chen, Jenny C, Darke, Paul L, Zugay, Joan A, Emini, Emilio A

Get full text

Benzocycloalkyl amines as novel C-termini for HIV protease inhibitors by Lyle, Terry A, Wiscount, Catherine M, Guare, James P, Thompson, Wayne J, Anderson, Paul S, Darke, Paul L, Zugay, Joan A, Emini, Emilio A, Schleif, William A

Get full text

Host Cell Factor Requirement for Hepatitis C Virus Enzyme Maturation by Waxman, Lloyd, Whitney, Michael, Pollok, Brian A., Kuo, Lawrence C., Darke, Paul L.

“…The cellular chaperone, HSP90, is identified here as an essential factor for the activity of NS2/3 protease of hepatitis C virus. The cleavage activity of…”
Get full text

Crystal structure at 1.9-A resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases by Chen, Z, Li, Y, Chen, E, Hall, D L, Darke, P L, Culberson, C, Shafer, J A, Kuo, L C

“…L-735,524 is a potent, orally bioavailable inhibitor of human immunodeficiency virus (HIV) protease currently in a Phase II clinical trial. We report here the…”
Get full text