Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease

Journal of Medicinal Chemistry

Volumn 43, Issue 19, 2000, Pages 3495-3504

  Tyndall, J D A ^a   Reid, R C ^a   Tyssen, D P ^b   Jardine, D K ^b   Todd, B ^c   Passmore, M ^a   March, D R ^a   Pattenden, L K ^a   Bergman, D A ^a   Alewood, D ^a   Hu, S H ^a   Alewood, P F ^a   Birch, C J ^b   Martin, J L ^a   Fairlie, D P ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b VICTORIAN INFECTIOUS DISEASES REFERENCE LABORATORY   (Australia)

^c ROYAL CHILDREN'S HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; INDINAVIR; MACROCYCLIC COMPOUND; PROTEINASE;

ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG STABILITY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; GENE MUTATION; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; PROTEIN CONFORMATION; PROTEIN STRUCTURE; SUBSTRATE PROCESSING; VIRION; VIRUS INFECTION; VIRUS REPLICATION;

ANTI-HIV AGENTS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; HETEROCYCLIC COMPOUNDS; HIV PROTEASE; HIV PROTEASE INHIBITORS; HIV-1; HIV-2; HUMANS; LEUKOCYTES, MONONUCLEAR; MODELS, MOLECULAR; MOLECULAR MIMICRY; PEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP; VIRUS REPLICATION;

EID: 0034699496     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000013n     Document Type: Article

References (42)

1. Structure-based inhibitors of HIV-1 protease
2. HIV protease as an inhibitor target for the treatment of AIDS
3. Targeting HIV-1 protease: A test of drug-design methodologies
4. HIV protease inhibitors
5. Inhibitors of HIV-1 protease: A major success of structure-assisted drug design
6. Therapeutic advances: Protease inhibitors for the treatment of HIV-1 infection
7. Viral genes and their products
8. The HIV-1 protease as enzyme and substrate: Mutagenesis of autolysis sites and generation of a stable mutant with retained kinetic properties
9. A nuclear localization signal within HIV-1 matrix protein that governs infection of nondividing cells
10. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection
11. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less
12. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors
13. Highly drug-resistant HIV-1 clinical isolates are cross-resistant to many antiretroviral compounds in current clinical development
14. Regioselective structural and functional mimicry of peptides: Design of hydrolytically stable cyclic peptidomimetic inhibitors of HIV 1 protease
15. Substrate based cyclic peptidomimetics of phe ile val that inhibit HIV 1 protease using a novel enzyme binding mode
16. A novel bicyclic enzyme inhibitor as a consensus peptidomimetic for the receptor-bound conformations of 12 peptidic inhibitors of HIV-1 protease
17. Crystal structure of HIV-1 protease in complex with VX-478 a potent and orally bioavailable inhibitor of the enzyme
18. 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
19. Novel binding mode of highly potent HIV-proteinase inhibitors incorporating the (R)-hydroxyethylamine isostere
20. Synthesis of conformationally restrained cyclic mimetics of HIV-1 protease substrates. Templates for combinatorial development of protease inhibitors
21. Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease
22. Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions
23. X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor
24. Conformational homogeneity in molecular recognition by proteolytic enzymes
25. Enzymatic activity of a synthetic 99 residue protein corresponding to the putative HIV-1 protease
26. Kinetic-properties of HIV-1 protease produced by total chemical synthesis with cysteine residues replaced by isosteric L-alpha-amino-N-butyric acid
27. Investigation of topoisomerase inhibitors for activity against human immunodeficiency virus: Inhibition by coumermycin A1
28. Isolation of HIV from Australian patients with AIDS, AIDS-related conditions and healthy antibody positive individuals
29. Cleavage of structural proteins during the assembly of the head of bacteriophage T4
30. Processing of X-ray diffraction data collected in oscillation mode
31. Assessment of phase accuracy by cross validation: The free R value. Methods and applications
32. Improved methods for building protein models in electron density maps and the location of errors in these models
33. Accurate bond and angle parameters for X-ray protein structure refinement
34. PROCHECK: A program to check the stereochemical quality of protein structures
35. WHAT CHECK (verification routines from WHAT IF). Errors in protein structures
36. SETOR: Hardware-lighted three-dimensional solid model representations of macromolecules
37. The protein data bank
38. Conformational selection of inhibitors and substrates by proteolytic enzymes: Implications for drug design and polypeptide processing
39. Database of three-dimensional structures of HIV proteinases
40. Traitment statistique des erreurs dans la determination des structures cristallines