Structure-based HIV-1 integrase inhibitor design: A future perspective

Expert Opinion on Investigational Drugs

Volumn 10, Issue 2, 2001, Pages 281-296

  Neamati, N ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Drug discovery; HIV 1 integrase; Inhibitors; Structure based drug design

Indexed keywords

1 [5 CHLOROINDOL 3 YL] 3 HYDROXY 3 [2H TETRAZOL 5 YL] PROPENONE; 4 [1 (4 FLUOROBENZYL) 2 PYRROLYL] 2,4 DIOXOBUTYRIC ACID; AROMATIC COMPOUND; CARBOXYLIC ACID DERIVATIVE; CICHORIC ACID; INDOLE DERIVATIVE; INTEGRASE; INTEGRASE INHIBITOR; L 708906; L 731927; L 731942; LIGANOLIDE; M 1541; NAPHTHALENE DERIVATIVE; NAPHTHALENE DISULPHONATE; NSC 103668; NSC 114690; NSC 134142; NSC 134144; NSC 134191; NSC 97318; PROTEINASE; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; ROSMARINIC ACID; S 153Y; TETRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZIDOVUDINE DERIVATIVE;

ARTICLE; COMBINATION CHEMOTHERAPY; DRUG APPROVAL; DRUG BINDING SITE; DRUG DESIGN; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME STRUCTURE; FOOD AND DRUG ADMINISTRATION; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; STRUCTURAL GENE; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANTI-HIV AGENTS; BINDING SITES; CATALYSIS; DNA; DRUG DESIGN; ENZYME INHIBITORS; HIV INTEGRASE; MOLECULAR SEQUENCE DATA;

EID: 0035147120     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.10.2.281     Document Type: Article

References (82)

1. HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer
2. Integration
3. Host proteins in retroviral cDNA integration
4. Nuclear import of human immunodeficiency virus type-1 preintegration complexes
5. Characterization of HIV replication complexes early after cell-to-cell infection
6. Association of integrase, matrix and reverse transcriptase antigens of human immunodeficiency virus Type 1 with viral nucleic acids following acute infection
7. Determination of viral proteins present in the human immunodeficiency virus Type 1 preintegration complex
8. Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules
9. Design and discovery of HIV-1 integrase inhibitors
10. HIV-1 integrase inhibitors: Past, present and future
11. Inhibitors of human immunodeficiency virus integrase
12. Retroviral integrase inhibitors year 2000: Update and perspectives
13. Inhibitors of strand transfer that prevent integration and inhibit HIV- 1 replication in cells
14. HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase
15. Nucleophile selection for the endonuclease activities of human, ovine and avian retroviral integrases
16. 2+ binding to the active site of EcoRV endonuclease: A crystallographic study of complexes with substrate and product DNA at 2 A resolution
17. Binding of different divalent cations to the active site of avian sarcoma virus integrase and their effects on enzymatic activity
18. 2+ binding site of P-type ion motive ATPases and the mechanism of phosphoryl group transfer
19. Structural basis for the 3′-5′ exonuclease activity of Escherichia coli DNA polymerase I: A two metal ion mechanism
20. The high resolution crystal structure of the DNA decamer d(AGGCATGCCT)
21. Crystal structures of catalytic core domains of retroviral integrases and role of divalent cations in enzymatic activity
22. HIV-1 integrase: Structural organization, conformational changes and catalysis
23. Cell protein cross-linking by erbstatin and related compounds
24. HIV cDNA integration: Molecular biology and inhibitor development
25. HIV integrase: A target for AIDS therapeutics
26. Molecular mechanisms in retrovirus DNA integration
27. HIV-1 integrase as a target for antiviral drugs
28. Retroviral cDNA integration: Mechanism, applications and inhibition
29. HIV integrase: The next target?
30. AntiHIV-1 integrase drugs: How far from the shelf?
31. Crystal structure of the catalytic domain of HIV-1 integrase: Similarity to other polynucleotidyl transferases
32. The catalytic domain of human immunodeficiency virus integrase: Ordered active site in the F185H mutant
33. Crystal structures of the catalytic domain of HIV-1 integrase free and complexed with its metal co-factor: High level of similarity of the active site with other viral integrases
34. Three new structures of the core domain of HIV-1 integrase: An active site that binds magnesium
35. Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: A model for viral DNA binding
36. High-resolution structure of the catalytic domain of avian sarcoma virus integrase
37. Atomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant
38. X-ray structure of simian immunodeficiency virus integrase containing the core and c-terminal domain (residues 50-293) - An initial glance of the viral dna binding platform
39. Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor
40. Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design
41. Pharmacophore perception, development and use in drug design
42. HIV-1 integrase pharmacophore: Discovery of inhibitors through three-dimensional database searching
43. Discovery of HIV-1 integrase inhibitors by pharmacophore searching
44. Identification of HIV-1 integrase inhibitors based on a four-point pharmacophore
45. Depsides and depsidones as inhibitors of HIV-1 integrase: Discovery of novel inhibitors through 3D database searching
46. Potent inhibitors of human immunodeficiency virus Type 1 integrase: Identification of a novel four-point pharmacophore and tetracyclines as novel inhibitors
47. Developing a dynamic pharmacophore model for HIV-1 integrase
48. Identification of the antiviral nucleoside drug binding site of HIV-1 integrase by proteolytic peptide mapping
49. Identification of a nucleotide binding site in HIV-1 integrase
50. Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus Type 1 integrase-DNA complex
51. Mapping features of HIV-1 integrase near selected sites on viral and target DNA molecules in an active enzyme-DNA complex by photo-cross- linking
52. Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking
53. HIV integrase structure and function
54. Human immuno-deficiency virus glycoprotein gp120 as the primary target for the antiviral action of AR177 (Zintevir)
55. Viral entry as the primary target for the antiHIV activity of chicoric acid and its tetra-acetyl esters
56. Identification of HIV-1 integrase inhibitors via three-dimensional database searching using ASV and HIV-1 integrases as targets
57. Active site binding modes of HIV-1 integrase inhibitors
58. Solution structure of the N-terminal zinc binding domain of HIV-1 integrase
59. Solution structure of the His 12-> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium
60. The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: A three-helix bundle stabilized by zinc
61. Refined solution structure of the dimeric N-terminal HHCC domain of HIV-2 integrase
62. Zinc fingers are sticking together
63. Genetic analysis of human immunodeficiency virus Type 1 integrase and the U3 att site: Unusual phenotype of mutants in the zinc finger-like domain
64. Lack of infectivity of HIV-1 integrase zinc finger-like domain mutant with morphologically normal maturation
65. Lessons from zinc-binding peptides
66. Physical basis of a protein-DNA recognition code
67. Virus-encoded zinc fingers as targets for antiviral chemotherapy
68. Building zinc fingers by selection: Toward a therapeutic application
69. An inhibitory monoclonal antibody binds at the turn of the HTH motif in the N-terminal domain of HIV-1 integrase
70. The DNA-binding domain of HIV-1 integrase has an SH3-like fold
71. Refined solution structure of the C-terminal DNA-binding domain of human immunovirus-1 integrase
72. Solution structure of the DNA binding domain of HIV-1 integrase
73. SH2 and SH3 domains: Potential targets for anticancer drug design
74. Complementation of integrase function in HIV-1 virions
75. Inhibition of human immunodeficiency virus Type 1 reverse transcriptase dimerization using synthetic peptides derived from the connection domain
76. The inhibition of human immunodeficiency virus proteases by 'interface peptides'
77. Triterpenes as potential dimerization inhibitors of HIV-1 protease
78. Engineering human immunodeficiency virus 1 protease heterodimers as macromolecular inhibitors of viral maturation
79. Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry
80. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway
81. Viral protein R regulates nuclear import of the HIV-1 pre-integration complex
82. Reduced nuclear import of human immunodeficiency virus Type 1 preintegration complexes in the presence of a prototypic nuclear targeting signal