Designing non-peptide peptidomimetics in the 21st century: Inhibitors targeting conformational ensembles

Journal of Medicinal Chemistry

Volumn 45, Issue 3, 2002, Pages 541-558

  Bursavich, Matthew G ^a   Rich, Daniel H ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; ASPARTIC PEPTIDASE INHIBITOR; BETA SECRETASE; CHYMOSIN; CP 113971; ENZYME INHIBITOR; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; INDINAVIR; JG 365; LOPINAVIR; NELFINAVIR; PENICILLOPEPSIN; PEPTIDASE; PEPTIDE DERIVATIVE; PROTEINASE INHIBITOR; RENIN INHIBITOR; RITONAVIR; SAQUINAVIR; U 85548E; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ALZHEIMER DISEASE; CATALYST; COMPUTER AIDED DESIGN; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG DESIGN; DRUG RECEPTOR BINDING; ENZYME ACTIVE SITE; ENZYME INHIBITOR INTERACTION; HYPERTENSION; LIGAND BINDING; MALARIA; MONTE CARLO METHOD; REACTION ANALYSIS; REVIEW;

ASPARTIC ENDOPEPTIDASES; BINDING SITES; DRUG DESIGN; ENZYME INHIBITORS; LIGANDS; MODELS, MOLECULAR; MOLECULAR MIMICRY; PEPTIDES; PROTEASE INHIBITORS; PROTEIN BINDING; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037203973     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm010425b     Document Type: Review

References (134)

1. Einfluss der configuration auf die wirkung der enzyme
2. Application of a theory of enzyme specificity to protein synthesis
3. Folding funnels and conformational transitions via hinge-bending motions
4. Folding funnels and binding mechanisms
5. Folding funnels, binding funnels, and protein function
6. Conformational analysis
7. Stereochemical aspects of drug action I: Conformational restriction, steric hindrance and hydrophobic collapse
8. Formation of the secondary and tertiary structure of enzymes
9. Protein three-dimensional structure and molecular recognition: A story of soft locks and keys
10. Conformational selection of inhibitors and substrates by proteolytic enzymes: Implications for drug design and polypeptide processing
11. Design, synthesis, and crystal structure of a pyrrolinone-based peptidomimetic possessing the conformation of a β-strand: Potential application to the design of novel inhibitors of proteolytic enzymes
12. Pyrrolinone-based HIV protease inhibitors. Design, synthesis, and antiviral activity: Evidence for improved transport
13. The mechanism of the catalytic action of pepsin and related acid proteinases
14. The active site of aspartic proteinases
15. Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: Implications for a mechanism of action
16. Crystallographic analysis of transition state mimics binding to penicillopepsin: Difluorostatine- and difluorostatone-containing peptides
17. Human immunodeficiency virus-1 protease. 2. Use of pH rate studies and solvent kinetic isotope effects to elucidate details of chemical mechanism
18. Role of conformational fluctuations in the enzymatic reaction of HIV- 1 protease
19. Follow the protons: A low-barrier hydrogen bond unifies the mechanisms of the aspartic proteases
20. Conformational flexibility of the catalytic Asp dyad in HIV-1 protease: An ab initio study on the free enzyme
21. Ab initio molecular dynamics-based assignment of the protonation state of pepstatin A/HIV-1 protease cleavage site
22. Solvent isotope effects on the onset of inhibition of porcine pepsin by pepstatin
23. Transpeptidation by porcine pepsin catalyzed by a noncovalent intermediate unique to its isomechanism
24. Peptidase inhibitors
25. Pepstatin, a new pepsin inhibitor produced by acetinomycetes
26. Mechanism of inhibition of pepsin by pepstatin
27. Structure-activity relations of antagonists of the renin-angiotensin system
28. Mode of inhibition of acid proteases by pepstatin
29. Pepstatin-derived inhibitors of aspartic proteinases. A close look at an apparent transition-state analog inhibitor
30. Novel transition-state analog inhibitors of renin
31. Synthesis of hydroxyethylene and ketomethylene dipeptide isosteres
32. Renin inhibitors
33. Design of peptide derived amino alcohols as transition-state analog inhibitors of angiotensin converting enzyme
34. Hydroxyethylamine analogs of the p17/p24 substrate cleavage site are tight-binding inhibitors of HIV protease
35. Approaches to the design of effective HIV-1 protease inhibitors
36. Protease inhibitors: Current status and future prospects
37. Structure-based drug design: The discovery of novel nonpeptide orally active inhibitors of human renin
38. In search of ideal antihypertensive drugs: Progress in five decades
39. Peptidomimetic design
40. Peptide backbone modifications: A structure-activity analysis of peptides containing amide bond surrogates, conformational constraints, and related backbone replacements
41. Stereochemical aspects of drug action I: Conformational restriction, steric hindrance and hydrophobic collapse
42. Bridging the gap between bioactive peptides and nonpeptides: Some perspectives in design
43. Partially modified retro-inverso peptides: Development, synthesis, and conformational behaviour
44. Concepts and progress in the development of peptide mimetics
45. From peptides to non-peptide peptidomimetics: Design and synthesis of new piperidine inhibitors of aspartic peptidases
46. Regioselective structural and functional mimicry of peptides. Design of hydrolytically stable cyclic peptidomimetic inhibitors of HIV-1 protease
47. Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease
48. Design principles for orally active drugs
49. Structure-based design on HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors
50. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors
51. Renin inhibition by substituted piperidines: A novel paradigm for the inhibition of monomeric aspartic proteinases?
52. Mechanism of acid protease catalysis based on the crystal strucutre of penicillopepsin
53. Conformational flexibility in the active sites of aspartyl proteinases revealed by a pepstatin fragment binding to penicillopepsin
54. 2 on inhibition of porcine pepsin
55. Three-dimensional structure of the complex of the Rhizopus chinensis carboxyl proteinase and pepstatin at 2.5 Å resolution
56. Structure and refinement of penicillopepsin at 1.8 Å resolution
57. Long-range electrostatic effects in pepsin catalysis
58. Crystal structures of native and inhibited forms of human cathepsin D: Implications for lysosomal targeting and drug design
59. X-ray analyses of aspartic proteinases IV. Structure and refinement at 2.2 A resolution of bovine chymosin
60. The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution
61. A 2.3 Å resolution structure of chymosin complexed with a reduced bond inhibitor shows that the active site beta-hairpin flap is rearranged when compared with the native crystal structure
62. Aspartic proteinases: The structures and functions of a versatile superfamily of enzymes
63. High-resolution X-ray diffraction study of the complex between endothiapepsin and an oligopeptide inhibitor: The analysis of the inhibitor binding and description of the rigid body shift in the enzyme
64. Domain flexibility in aspartic proteinases
65. Revised 2.3 Å structure of porcine pepsin: Evidence for a flexible domain
66. Structure of a pepsin/penin inhibitor complex reveals a novel crystal packing induced by minor chemical alterations in the inhibitor
67. The dependence of enzyme inhibition of the distribution of enzyme forms. Implications for substrate and inhibitor structure-activity correlations
68. HIV therapy advances. Update on a proteinase inhibitor
69. Safety and activity of saquinavir in HIV infection
70. Molecular recognition of protein-ligand complexes: Applications to drug design
71. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Å resolution
72. X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor
73. The road to Fortovase. A history of saquinavir, the first human immunodeficiency virus protease inhibitor
74. Novel binding mode of highly potent HIV-proteinase inhibitors incorporating the (R)-hydroxyethylamine isostere
75. Effect of hydroxyl group configuration in hydroxyethylamine dipeptide isosteres on HIV protease inhibition. Evidence for multiple binding modes
76. Inhibition of aspartic proteases by pepstatin and 3-methylstatine derivatives of pepstatin. Evidence for collected-substrate enzyme inhibition
77. 2′ structure-activity relationship, and molecular recognition of cyclic ureas
78. Cyclic HIV protease inhibitors capable of displacing the active site structural water molecule
79. NMR and X-ray evidence that the HIV protease catalytic aspartyl groups are protonated in the complex formed by the protease and a non-peptide cyclic urea-based inhibitor
80. 4-hydroxy-5,6-dihydropyrones. 2. Potent non-peptide inhibitors of HIV protease
81. Tipranavir (PNU-140690): A potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class
82. Piperidine-renin inhibitors compounds with improved physico-chemical properties
83. Substituted piperidines-highly potent renin inhibitors due to induced fit adaptation of the active site
84. Piperidine renin inhibitors: From leads to drug candidates
85. Potent in vivo inhibitors of rat renin: Analogs of human and rat angiotensinogen sequences containing different classes of pseudodipeptides at the scissile site
86. New renin inhibitors containing novel analogs of statine
87. Engineering enzyme specificity by "substrate-assisted catalysis"
88. Multiple highly diverse structures complementary to enzyme binding sites: Results of extensive application of a de novo design method incorporating combinatorial growth
89. The art and practice of structure-based drug design: A molecular modeling perspective
90. Combinatorial design and combinatorial synthesis of enzyme inhibitors
91. Merging rational drug design with combinatorial chemistry: Reasonable and unreasonable expectations
92. Synthesis of novel cyclic protease inhibitors using Grubbs olefin metathesis
93. Design and synthesis of unsymmetrical peptidyl urea inhibitors of aspartic peptidases
94. Aspartic protease inhibitors designed from computer-generated templates bind as predicted
95. Approaches to solving the rigid receptor problem by identifying a minimal set of flexible residues during ligand docking
96. Virtual screening with solvation and ligand-induced complementarity
97. Method for including the dynamic fluctuations of a protein in computer-aided drug design
98. Accommodating protein flexibility in computational drug design
99. Molecular docking to ensembles of protein structures
100. DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases
101. Parallel simulated tempering dynamics of ligand-protein binding with ensembles of protein conformations
102. Computer simulations of ligand-protein binding with ensembles of protein conformations: A monte carlo study of HIV-1 protease binding energy landscapes
103. Modern computational chemistry and drug discovery: Structure generating programs
104. GREEN - A package program for docking studies in rational drug design
105. CAVEAT: A program to facilitate the design of organic molecules
106. HOOK: A program for finding novel molecular architectures that satisfy the chemical and steric requirements of a macromolecule binding site
107. LUDI: Rule-based automatic design of new substituents for enzyme inhibitor leads
108. The computer program LUDI: A new method for the de novo design of enzyme inhibitors
109. The NEWLEAD program: A new method for the design of candidate structures from pharmacophoric hypotheses
110. SPLICE: A program to assemble partial query solutions from three-dimensional database searches into novel ligands
111. HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility
112. Computer design of bioactive molecules: A method for receptor-based de novo ligand design
113. GroupBuild: A fragment-based method for de novo drug design
114. A novel method for the modeling of peptide ligands to their receptors
115. Automatic creation of drug candidate structures based on receptor structure. Starting point for artificial lead generation
116. GenStar: Method for de novo drug design
117. Peptidomimetics derived from natural products
118. Two-state allosteric behavior in a single-domain signaling protein
119. A hot spot of binding energy in a hormone-receptor interface
120. Conformation of a peptide ligand bound to its G-protein coupled receptor