A personal account of the role of peptide research in drug discovery: The case of hepatitis C1

Journal of Peptide Science

Volumn 7, Issue 1, 2001, Pages 2-14

  Pessi, Antonello ^a  

^a IRBM   (Italy)

Author keywords

Drug discovery; Hepatitis C

Indexed keywords

FLUORESCENT DYE; MEMBRANE PROTEIN; PEPTIDE; PROTEIN INHIBITOR; PROTEINASE; SERINE; VIRUS PROTEIN;

ASSAY; BINDING AFFINITY; CHEMICAL PROCEDURES; DRUG RESEARCH; ENZYME ACTIVATION; ENZYME BINDING; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYMOLOGY; GENETIC ENGINEERING; HEPATITIS C; HEPATITIS C VIRUS; ITALY; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROCESSING; REVIEW; SCREENING; SOLUBILITY; STRUCTURE ANALYSIS; VARIANCE;

BINDING SITES; DRUG DESIGN; HEPACIVIRUS; HUMANS; MODELS, MOLECULAR; PEPTIDES; RNA HELICASES; SERINE ENDOPEPTIDASES; SUBSTRATE SPECIFICITY; TECHNOLOGY, PHARMACEUTICAL; VIRAL NONSTRUCTURAL PROTEINS;

HEPATITIS C VIRUS;

EID: 0035112985     PISSN: 10752617     EISSN: None     Source Type: Journal    
DOI: 10.1002/psc.310     Document Type: Review

References (82)

1. Assessing the protease and protease inhibitor content of the human genome
2. Hepatitis C viruses
3. Hepatitis C virus: Epidemiology, transmission and prevention
4. Hepatitis C: The clinical spectrum of disease
5. Hepatitis C virus NS3/4A protease
6. The proteinases encoded by hepatitis C virus as therapeutic targets
7. The molecular virology of hepatitis C
8. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins
9. Kinetic and structural analyses of hepatitis C virus polyprotein processing
10. A central region in the hepatitis C virus NS4A protein allows formation of an active NS3-NS4A serine proteinase complex in vivo and in vitro
11. Hepatitis C virus-encoded nonstructural protein NS4A has versatile functions in viral protein processing
12. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site
13. Crystal structure of the hepatitis virus NS3 proteinase domain complexed with a synthetic NS4A cofactor peptide
14. Complex of NS3 proteinase and NS4A peptide of BK strain hepatitis C virus: A 2.2 Å resolution structure in a hexagonal crystal form
15. Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase
16. Two proteinase activities in HCV polypeptide expressed in insect cells using baculovirus vector
17. In vitro cleavage of hepatitis C virus polyprotein substrates by purified recombinant NS3 protease
18. In vitro activity of hepatitis C virus protease NS3 purified from recombinant baculovirus-infected Sf9 cells
19. Activity of purified hepatitis C virus proteinase NS3 on peptide substrates
20. A central region in the hepatitis C virus NS4A protein allows formation of an active NS3-NS4A serine proteinase complex in vivo and in vitro
21. In vitro studies on the activation of the hepatitis C virus NS3 proteinase by the NS4A cofactor
22. Enhancement of hepatitis C virus NS3 proteinase activity by association with NS4A-specific synthetic peptides: Identification of sequence and critical residues of NS4A for the cofactor activity
23. Identification of the sequence of NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 proteinase
24. Serine protease of hepatitis C virus expressed in insect cells as the NS3/4A complex
25. Multiple enzymatic activities associated with recombinant NS3 protein of hepatitis C virus
26. Engineering, characterization and phage-display of hepatitis C virus NS3 protease and NS4A cofactor peptide as a single chain protein
27. Rational design and functional expression of a constitutively active single-chain NS4A-NS3 proteinase
28. Probing the substrate specificity of hepatitis C virus NS3 serine proteinase by using synthetic peptides
29. Substrate specificity of the hepatitis C virus serine proteinase NS3
30. Mechanistic role of an NS4A peptide cofactor with the truncated NS3 proteinase of hepatitis C virus: Elucidation of the NS4A stimulatory effect via kinetic analysis and inhibitor mapping
31. Product inhibition of the hepatitis C virus NS3 proteinase
32. Potent peptide inhibitors of human hepatitis C virus NS3 proteinase are obtained by optimizing the cleavage products
33. Peptide-based inhibitors of the hepatitis C virus serine protease
34. 1 cysteine for substrate and inhibitors of the hepatitis C virus NS3 serine protease. Potent, reversible, covalent and non-covalent competitive inhibitors
35. Chetoacids are potent slow binding inhibitors of the hepatitis C virus NS3 protease
36. Inhibition of the hepatitis C virus NS3/4A protease. The crystal structure of two protease-inhibitor complexes
37. Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain
38. Probing the active site of the hepatitis C virus serine protease by fluorescence resonance energy transfer
39. Molecular model of the specificity pocket of the hepatitis C virus proteinase: Implications for substrate recognition
40. Amino-aromatic interactions in proteins
41. Aromatic rings act as hydrogen bond acceptors
42. Specificity of the hepatitis C virus NS3 serine protease: Effects of substitutions at the 3/4A, 4A/4B, 4B/5A, and 5A/5B cleavage sites on polyprotein processing
43. Substrate determinants for cleavage in cis and in trans by the hepatitis C virus NS3 proteinase
44. Structural characterization of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein by NMR and modeling studies
45. Solution structure of substrate-based ligands when bound to hepatitis C virus NS3 protease domain
46. NS3-4A of hepatitis C virus is a chymotrypsin-like protease
47. An in vitro assay for hepatitis C virus NS3 serine proteinase
48. HIV-1 protease specificity derived from a complex mixture of synthetic substrates
49. Peptide substrate cleavage specificity of the human cytomegalovirus protease
50. Purification of active herpes simplex virus-1 protease expressed in Escherichia coli
51. Synthetic depsipeptide substrates for the assay of human hepatitis C virus protease
52. A high-throughput radiometric assay for hepatitis C virus NS3 protease
53. A continous assay of hepatitis C virus protease based on resonance energy transfer depsipeptide substrates
54. An improved solid-phase synthesis of resonance energy transfer fluorescent peptides and depsipeptides employing the EDANS/DABCYL donor-acceptor pair
55. Hepatitis C virus: An overview of current approaches and progress
56. Role of the S subsites in serine protease catalysis. Active-site mapping of rat chymotrypsin, rat trypsin, α-lytic protease, and cercarial protease from Schistosoma mansoni
57. Structures of product and inhibitor complexes of Streptomyces griseus protease A at 1.8 Å resolution. A model for serine protease catalysis
58. Refined structure of Sindbis virus core protein and comparison with other chymotrypsin-like serine proteinase structures
59. Structure-based understanding of ligand affinity using human thrombin as a model system
60. Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease
61. Conformational changes in human hepatitis C virus NS3 protease upon binding of product-based inhibitors
62. α-chetoamides, α-chetoesters and α-dichetones as HCV NS3 protease inhibitors
63. Solid phase synthesis of peptide aldehyde protease inhibitors. Probing the proteolytic sites of hepatitis C virus polyprotein
64. N-Benzyloxycarbonyl-valyl-prolinal, a potent inhibitor of post-proline cleaving enzyme
65. Highly selective tripeptide thrombin inhibitors
66. Complex formation between the hepatitis C virus serine protease and a synthetic NS4A cofactor peptide
67. The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism
68. Topology of the calmodulin-melittin complex
69. Conformational changes in the NS3 protease from hepatitis C virus strain Bk monitored by limited proteolysis and mass spectrometry
70. Multiple determinants influence complex formation of the hepatitis C virus NS3 protease domain with its NS4A cofactor peptide
71. Characterization of the human cytomegalovirus protease as an induced-fit serine protease and the implications to the design of mechanism-based inhibitors
72. Engineering and chemical synthesis of a transmembrane protein: The HCV protease cofactor NS4A
73. Chemical synthesis of peptides and proteins
74. High level expression and rational mutagenesis of a designed protein, the minibody
75. Synthesis of proteins by native chemical ligation
76. A zinc binding site in viral serine proteinases
77. The metal binding site of the hepatitis C virus NS3 proteinase. A spectroscopic investigation
78. Optimization of the P′-region of peptide inhibitors of hepatitis C virus NS3/4A protease
79. The role of charged residues in the catalytic mechanism of the hepatitis C virus NS3 protease: Electrostatic pre-collision guidance and transition state stabilization