The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives

Smith, David George Emslie; Gribble, Andrew D.; Haigh, David; Ife, Robert J.; Lavery, Patrick; Skett, Peter W.; Slingsby, Brian P.; Stacey, Rachel; Ward, Robert W.; West, Andrew B.

doi:10.1016/s0960-894x(99)00539-9

Cited by 21 publications

(4 citation statements)

References 17 publications

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“…IC 50 values of several compounds in this series are in the low nanomolar range [114]. It remains to be studied if these compounds offer wide enough therapeutic window, namely high enough ratio of TC 50 over IC 50 , specificity and stability toward biologically relevant non-specific nucleophilic attack.…”

Section: H Current Activity In Drug Discoverymentioning

confidence: 96%

Impact of Recombinant DNA Technology and Protein Engineering on Structure-Based Drug Design: Case Studies of HIV-1 and HCMV Proteases

Kan

2002

CTMC

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Structure-based drug design is an organized, multidisciplinary endeavor undertaken by scientists from many different scientific fields. The success of structure-based drug design was only made possible by advances in structure biology that provides the three-dimensional structure of the drug design target with which small molecular chemical ligands interact. Visualization of the conformation and interactions of a small molecule ligand bound to the protein target in the co-crystal structure of the protein:ligand complex enables the design of new chemical compounds with improved binding affinity and specificity. With the advances in molecular biology, lab automation, and computational science, genomic data have now become available for the human genome, as well as various other organisms. The pharmaceutical industry is currently putting forth tremendous effort in the area of functional genomics and structural genomics in attempts to decipher functions and structures of protein encoded by genes, with the ultimate goal of identifying novel targets for drug discovery and development. This chapter discusses the significant impact made by recombinant DNA technology and protein engineering on structural biology and, more specifically, on structure-based drug design.

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Section: H Current Activity In Drug Discoverymentioning

confidence: 96%

Impact of Recombinant DNA Technology and Protein Engineering on Structure-Based Drug Design: Case Studies of HIV-1 and HCMV Proteases

Kan

2002

CTMC

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“…114 Incorporation of moieties with H-bonding potential in an attempt to increase potency vs. the enzyme, led to the thienoxazinone derived nitroso and hydroxylamine compounds (72,73) which are some of the most potent, non-peptide inhibitors of HCMV protease prepared to date. 115 The inhibition of the enzyme is through 1:1 adducts at Ser 132, although the reason for the increased potency of these last compounds has not been de®nitively established.…”

Section: Hcmv Protease Inhibitorsmentioning

confidence: 99%

Recent strategies in the development of new human cytomegalovirus inhibitors

Martı́nez¹,

Castro²,

Gil³

et al. 2001

Medicinal Research Reviews

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Human cytomegalovirus (HCMV) is one of the most common opportunistic infections in immunucompromised individuals, such as AIDS patients and organ transplant recipients, and is the most frequent congenital viral infection in humans. Despite a reduction of the incidence of AIDS‐related opportunistic infections in patients under highly active antiretroviral treatment, attention should be paid to the HCMV risk factor in these individuals. Furthermore, HCMV may have an important role in atherosclerosis. Existing antiviral treatments for the HCMV infection suffer from poor bioavailability, toxicity, and limited effectiveness, mainly due to the development of drug resistance. Fortunately there are novel and potentially very effective new compounds undergoing pre‐clinical and clinical evaluation. This review provides an overview in the last five years of new HCMV inhibitors (chemical structures, SAR, and new mechanisms of action) with the aim to provide new clues for the development of future drugs against this opportunistic virus. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 3, 227–244, 2001

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“…As a result, in an effort to identify inhibitors with novel mechansims of action, a number of laboratories have sought inhibitors of the essential protease encoded by the HCMV UL80 gene as potentially effective antiviral chemotherapeutic agents. Thus far, several mechanism and peptide-based inhibitors of this enzyme have been disclosed [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Green Synthesis of Tetrazines and their Role as Human Cytomegalovirus (HCMV) Protease Inhibitor

Singh¹,

Kumari²

2016

J Theor Comput Sci

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The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives

Cited by 21 publications

References 17 publications

Impact of Recombinant DNA Technology and Protein Engineering on Structure-Based Drug Design: Case Studies of HIV-1 and HCMV Proteases

Impact of Recombinant DNA Technology and Protein Engineering on Structure-Based Drug Design: Case Studies of HIV-1 and HCMV Proteases

Recent strategies in the development of new human cytomegalovirus inhibitors

Green Synthesis of Tetrazines and their Role as Human Cytomegalovirus (HCMV) Protease Inhibitor

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