The most potent organophosphorus inhibitors of leucine aminopeptidase. Structure-based design, chemistry, and activity

Journal of Medicinal Chemistry

Volumn 46, Issue 13, 2003, Pages 2641-2655

  Grembecka, Jolanta ^a   Mucha, Artur ^a   Cierpicki, Tomasz ^b   Kafarski, Paweł ^a  

^a WROCLAW UNIVERSITY OF TECHNOLOGY   (Poland)

^b UNIVERSITY OF WROC AW   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOSOL AMINOPEPTIDASE; CYTOSOL AMINOPEPTIDASE INHIBITOR; DIPEPTIDE; ENZYME INHIBITOR; LEUCINE; MICROSOMAL AMINOPEPTIDASE; ORGANOPHOSPHORUS COMPOUND; PHOSPHINATE DERIVATIVE; PHOSPHONAMIDATE DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CHEMICAL MODIFICATION; COMPUTER ANALYSIS; COVALENT BOND; CRYSTAL STRUCTURE; DECOMPOSITION; DRUG ACTIVITY; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; ENZYME ACTIVE SITE; ENZYME BINDING; INHIBITION KINETICS; MOLECULAR STABILITY; PH; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIGENS, CD13; BINDING SITES; CATTLE; CRYSTALLOGRAPHY, X-RAY; DIPEPTIDES; DRUG STABILITY; ENZYME INHIBITORS; LENS, CRYSTALLINE; LEUCINE; LEUCYL AMINOPEPTIDASE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; ORGANOPHOSPHORUS COMPOUNDS; PHOSPHINIC ACIDS; PHOSPHONIC ACIDS; PROTEIN BINDING; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0038115341     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030795v     Document Type: Article

References (91)

1. Wlodawer, A.; Vondrasek, J. Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annu. Rev. Biophys. Biomol. Struct. 1998, 27, 249-284.
2. Amzel, L. M. Structure-based drug design. Curr. Opin. Biotechnol. 1998, 9, 366-369.
3. Marrone, T. J.; Briggs, J. M.; McCammon, J. A. Structure-based drug design: computational advances. Annu. Rev. Pharmacol. Toxicol. 1997, 37, 71-90.
4. Taylor, A. Aminopeptidases: towards a mechanism of action. Trends Biochem. Sci. 1993, 18, 167-171.
5. Taylor, A. Aminopeptidases: structure and function. FASEB J. 1993, 7, 290-298.
6. Buffone, G. J.; Spence, J. E.; Fernbach, S. D.; Curry, M. R.; O'Brien, W. E. et al. Prenatal diagnosis of cystic fibrosis: microvillar enzymes and DNA analysis compared. Clin. Chem. 1988, 34, 933-937.
7. Henson, H.; Frohne, M. Crystalline leucine aminopeptidase from lens (alpha-aminoacyl-peptide hydrolase; EC 3.4.11.1). Methods Enzymol. 1976, 45, 504-520.
8. Prescott, J. M.; Wilkes, S. H. Aeromonas aminopeptidase. Methods Enzymol. 1976, 45, 530-543.
9. Smith, E. L.; Hill, R. L. Leucine aminopeptidase. The enzymes; 2nd ed.; Academic Press: New York, 1960; pp 37-62.
10. Strater, N.; Lipscomb, W. N. Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site solvent structure and binding mode of L-leucinal, a gem-diolate transition state analogue, by X-ray crystallography. Biochemistry 1995, 34, 14792-14800.
11. Kim, H.; Lipscomb, W. N. Structure and mechanism of bovine lens leucine aminopeptidase. Adv. Enzymol. Relat. Areas Mol. Biol. 1994, 68, 153-213.
12. Strater, N.; Sun, L.; Kantrowitz, E. R.; Lipscomb, W. N. A bicarbonate ion as a general base in the mechanism of peptide hydrolysis by dizinc leucine aminopeptidase. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 11151-11155.
13. Umezawa, H. Screening of small molecular microbial products modulating immune responses and bestatin. Recent Results Cancer Res. 1980, 75, 115-125.
14. Gupta, S. K.; Aziz, M.; Khan, A. A. Serum leucine aminopeptidase estimation: a sensitive prognostic indicator of invasiveness in breast carcinoma. Indian J. Pathol. Microbiol. 1989, 32, 301-305.
15. Taylor, A.; Daims, M.; Lee, J.; Surgenor, T. Identification and quantification of leucine aminopeptidase in aged normal and cataractous human lenses and ability of bovine lens LAP to cleave bovine crystallins. Curr. Eye Res. 1982, 2, 47-56.
16. Taylor, A.; Brown, M. J.; Daims, M. A.; Cohen, J. Localization of leucine aminopeptidase in normal hog lens by immunofluorescence and activity assays. Invest. Ophthalmol. Vis. Sci. 1983, 24, 1172-1180.
17. Taylor, A.; Surgenor, T.; Thomson, D. K.; Graham, R. J.; Oettgen, H. Comparison of leucine aminopeptidase from human lens, beef lens and kidney, and hog lens and kidney. Exp. Eye Res. 1984, 38, 217-229.
18. Scott, C. S.; Davey, M.; Hamilton, A.; Norfolk, D. R. Serum enzyme concentrations in untreated acute myeloid leukaemia. Blut 1986, 52, 297-303.
19. Beninga, J.; Rock, K. L.; Goldberg, A. L. Interferon-gamma can stimulate post-proteasomal trimming of the N terminus of an antigenic peptide by inducing leucine aminopeptidase. J. Biol. Chem. 1998, 273, 18734-18742.
20. Pulido-Cejudo, G.; Conway, B.; Proulx, P.; Brown, R.; Izaguirre, C. A. Bestatin-mediated inhibition of leucine aminopeptidase may hinder HIV infection. Antiviral Res. 1997, 36, 167-177.
21. Taylor, A.; Volz, K. W.; Lipscomb, W. N.; Takemoto, L. J. Leucine aminopeptidase from bovine lens and hog kidney. Comparison using immunological techniques, electron microscopy, and X-ray diffraction. J. Biol. Chem. 1984, 259, 14757-14761.
22. Oettgen, H. C.; Taylor, A. Purification, preliminary characterization, and immunological comparison of hog lens leucine aminopeptidase (EC 3.4.11.1) with hog kidney and beef lens aminopeptidases. Anal. Biochem. 1985, 146, 238-245.
23. Grembecka, J.; Kafarski, P. Leucine aminopeptidase as a target for inhibitor design. Mini Rev. Med. Chem. 2001, 1, 133-144.
24. Giannousis, P. P.; Bartlett, P. A. Phosphorus amino acid analogues as inhibitors of leucine aminopeptidase. J. Med. Chem. 1987, 30, 1603-1609.
25. Strater, N.; Lipscomb, W. N. Transition state analogue Lleucinephosphonic acid bound to bovine lens leucine aminopeptidase: X-ray structure at 1.65 A resolution in a new crystal form. Biochemistry 1995, 34, 9200-9210.
26. Suda, H.; Aoyagi, T.; Takeuchi, T.; Umezawa, H. Inhibition of aminopeptidase B and leucine aminopeptidase by bestatin and its stereoisomer. Arch. Biochem. Biophys. 1976, 177, 196-200.
27. Kim, H.; Lipscomb, W. N. X-ray crystallographic determination of the structure of bovine lens leucine aminopeptidase complexed with amastatin: formulation of a catalytic mechanism featuring a gem-diolate transition state. Biochemistry 1993, 32, 8465-8478.
28. Kim, H.; Burley, S. K.; Lipscomb, W. N. Re-refinement of the X-ray crystal structure of bovine lens leucine aminopeptidase complexed with bestatin. J. Mol. Biol. 1993, 230, 722-724.
29. Burley, S. K.; David, P. R.; Sweet, R. M.; Taylor, A.; Lipscomb, W. N. Structure determination and refinement of bovine lens leucine aminopeptidase and its complex with bestatin. J. Mol. Biol. 1992, 224, 113-140.
30. Bohm, H. J. LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads. J. Comput.-Aided Mol. Des. 1992, 6, 593-606.
31. Bohm, H. J. A novel computational tool for automated structure-based drug design. J. Mol. Recognit. 1993, 6, 131-137.
32. Bohm, H. J. On the use of LUDI to search the Fine Chemicals Directory for ligands of proteins of known three-dimensional structure. J. Comput.-Aided Mol. Des. 1994, 8, 623-632.
33. Bohm, H. J. Towards the automatic design of synthetically accessible protein ligands: peptides, amides and peptidomimetics. J. Comput.-Aided. Mol. Des. 1996, 10, 265-272.
34. Grembecka, J.; Sokalski, W. A.; Kafarski, P. Computer-aided design and activity prediction of leucine aminopeptidase inhibitors. J. Comput.-Aided. Mol. Des. 2000, 14, 531-544.
35. Bartlett, P. A.; Hanson, J. E.; Archer, F.; Giannousis, P. P. Phosphorus analogues as peptidase inhibitors: aspartic peptidases and leucine aminopeptidase. 2nd International Symposium on Phosphorus Chemistry Directed Towards Biology; Elsevier Science Publishers B. V. Amsterdam, The Netherlands: Lodz, Poland, 1986.
36. Kafarski, P.; Lejczak, B. Aminophosphonic and Aminophosphinic Acids. Chemistry and Biological Activity; John Wiley & Sons: New York, 2000; pp 173-203 and 407-442.
37. Hirschmann, R.; Yager, K. M.; Taylor, C. M.; Witherington, J.; Sprengeler, P. A.; et al. Phosphonate diester and phosphonamide synthesis. Reaction coordinate analysis by 31P NMR spectroscopy: identification of phyrophosphonate anhydrides and highly recative phosphonylammonium salts. J. Am. Chem. Soc. 1997, 119, 8177-8190.
38. Malachowski, W. P.; Coward, J. K. The chemistry of phosphopeptides: formation of functionalized phosphonochloridates under mild conditions and their reaction with alcohols and amines. J. Org. Chem, 1994, 59, 7616-7624.
39. Mucha, A.; Kafarski, P.; Plenat, F.; Cristau, H.-J. The preparation of phosphonopeptides containing a phosphonamidate bond. Tetrahedron 1994, 50, 12743-12754.
40. Mookhtiar, K. A.; Marlowe, C. K.; Bartlett, P. A.; Van Wart, H. E. Phosphonamidate inhibitors of human neutrophil collagenase. Biochemistry 1987, 26, 1962-1965.
41. Hanson, J. E.; Kaplan, A. P.; Bartlett, P. A. Phosphonate analogues of carboxypeptidase A substrates are potent transition-state analogue inhibitors. Biochemistry 1989, 28, 6294-6305.
42. Yiotakis, A.; Lecoq, A.; Nicolaou, A.; Labadie, J.; Dive, V. Phosphinic peptide analogues as potent inhibitors of Corynebacterium rathayii bacterial collagenase. Biochem. J. 1994, 303, 323-327.
43. Yuan, W.; Munoz, B.; Wong, C. H.; Haeggstrom, J. Z.; Wetterholm, A. et al. Development of selective tight-binding inhibitors of leukotriene A4 hydrolase. J. Med. Chem. 1993, 36, 211-220.
44. Yang, K. W.; Brandt, J. J.; Chatwood, L. L.; Crowder, M. W. Phosphonamidate and phosphothioate dipeptides as potential inhibitors of VanX. Bioorg. Med. Chem. Lett. 2000, 10, 1085-1087.
45. Vo-Quang, Y.; Gravey, A. M.; Simonneau, R.; Vo-Quang, L.; Lacoste, A. M. et al. Towards new inhibitors of D-alanine: D-alanine ligase: The synthesis of 3-amino butenylphosphonic and aminophosphonamidic acids. Tetrahedron Lett. 1987, 28, 6167-6170.
46. Elhaddadi, M.; Jacquier, R.; Petrus, C.; Petrus, F. N-benzyloxyamino phosphinyl peptides. Phosphorus, Sulfur and Silicon 1991, 63, 255-259.
47. Bartlett, P. A.; Marlowe, C. K. Evaluation of intrinsic binding energy from a hydrogen bonding group in an enzyme inhibitor. Science 1987, 235, 569-571.
48. Matthews, B. W. Structural basis for the action of thermolysin and related zinc peptidases. Acc. Chem. Res. 1988, 21, 333-340.
49. Jacobsen, N. E.; Bartlett, P. A. A phosphonamidate dipeptide analogue as an inhibitor of carboxypeptidase A. J. Am. Chem. Soc. 1981, 103, 654-657.
50. Jacobsen, N. E.; Bartlett, P. A. Cyclic phosphonic-carboxylic imides and anhydrides as reactive intermaediates. 1. Rearrangement and solvolysis of N-(amino(methyl)phosphonyl)-L-phenylalanine derivatives. J. Am. Chem. Soc. 1983, 105, 1613-1619.
51. Jacobsen, N. E.; Bartlett, P. A. Cyclic phosphonic-carboxylic imides and anhydrides as reactive intermediates. 2. Solvolysis of N-(hydroxy(methyl)phosphinothioyl)-L-phenylalanine derivatives. J. Am. Chem. Soc. 1983, 110, 1619-1626.
52. Christianson, D. W.; Lipscomb, W. N. Structure of the complex between an unexpectedly hydrolyzed phosphonamidate inhibitor and carboxypeptidase A. J. Am. Chem. Soc. 1986, 108, 545-546.
53. Christianson, D. W.; Lipscomb, W. N. Comparison of carboxypeptidase A and thermolysin: inhibition by phosphonamidates. J. Am. Chem. Soc. 1988, 110, 5560-5565.
54. Lejczak, B.; Kafarski, P.; Zygmunt, J. Inhibition of aminopeptidases by aminophosphonates. Biochemistry 1989, 28, 3549-3555.
55. Grembecka, J.; Sokalski, W. A.; Kafarski, P. Quantum chemical analysis of the interactions of transition state analogues with leucine aminopeptidase. Int. J. Quantum. Chem. 2001, 84, 302- 310.
56. Collinsova, M.; Jiracek, J. Phosphinic acid compounds in biochemistry, biology and medicine. Curr. Med. Chem. 2000, 7, 629-647.
57. Grobelny, D.; Goli, U. B.; Galardy, R. E. Binding energetics of phosphorus-containing inhibitors of thermolysin. Biochemistry 1989, 28, 4948-4951.
58. Yiotakis, A.; Vassiliou, S.; Jiracek, J.; Dive, V. Protection of the hydroxyphosphinyl function of phosphinic dipeptides by adamantyl. Application to the solid-phase synthesis of phosphinic peptides. J. Org. Chem. 1996, 61, 6601-6605.
59. Vassiliou, S.; Mucha, A.; Cuniasse, P.; Georgiadis, D.; Lucet-Levannier, K. et al. Phosphinic pseudo-tripeptides as potent inhibitors of matrix metalloproteinases: a structure -activity study. J. Med. Chem. 1999, 42, 2610-2620.
60. Parsons, W. H.; Patchett, A. A.; Bull, H. G.; Schoen, W. R.; Taub, D. et al. Phosphinic acid inhibitors of D-alanyl-D-alanine ligase. J. Med. Chem. 1988, 31, 1772-1778.
61. Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. Renin inhibitors. Synthesis of transition-state analogue inhibitors containing phosphorus acid derivatives at the scissile bond. J. Med. Chem. 1989, 32, 1652-1661.
62. Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. 1-Aminoalkylphosphonous acids. Part 1. Isosteres of the protein amino acids. J. Chem. Soc., Perkin Trans. 1 1984, 2845-2853.
63. Chen, H.; Noble, F.; Mothe, A.; Meudal, H.; Coric, P. et al. Phosphinic derivatives as new dual enkephalin-degrading enzyme inhibitors: synthesis, biological properties, and antinociceptive activities. J. Med. Chem. 2000, 43, 1398-1408.
64. Taylor, A.; Peltier, C. Z.; Torre, F. J.; Hakamian, N. Inhibition of bovine lens leucine aminopeptidase by bestatin: number of binding sites and slow binding of this inhibitor. Biochemistry 1993, 32, 784-790.
65. Wilkes, S. H.; Prescott, J. M. The slow, tight binding of bestatin and amastatin to aminopeptidases. J. Biol. Chem. 1985, 260, 13154-13162.
66. Andersson, L.; Isley, T. C.; Wolfenden, R. Alpha-aminoaldehydes: transition state analogue inhibitors of leucine aminopeptidase. Biochemistry 1982, 21, 4177-4180.
67. Bohm, H. J. Prediction of binding constants of protein ligands: a fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J. Comput.-Aided Mol. Des. 1998, 12, 309-323.
68. Holden, H. M.; Tronrud, D. E.; Monzingo, A. F.; Weaver, L. H.; Matthews, B. W. Slow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues. Biochemistry 1987, 26, 8542-8553.
69. Tronrud, D. H.; Holden, H. M.; Matthews, B. W. Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bodn. Science 1987, 571-574.
70. Grams, F.; Dive, V.; Yiotakis, A.; Yiallouros, I.; Vassiliou, S. et al. Structure of astacin with a transition-state analogue inhibitor. Nat. Struct. Biol. 1996, 3, 671-675.
71. Gall, A. L.; Ruff, M.; Kannan, R.; Cuniasse, P.; Yiotakis, A. et al. Crystal structure of the stromelysin-3 (MMP-11) catalytic domain complexed with a phosphinic inhibitor mimicking the transition-state. J. Mol. Biol. 2001, 307, 577-586.
72. Radkiewicz, J. L.; McAllister, M. A.; Goldstein, E.; Houk, K. N. A theoretical investigation of phosphonamidates and sulfonamides as protease transition state isosters. J. Org. Chem. 1998, 63, 1419-1428.
73. Malachowski, W. P.; Coward, J. K. The chemistry of phosphapeptides: investigations on the synthesis of phosphonamidate, phosphonate and phosphinate analogues of glutamyl-γglutamate. J. Org. Chem. 1994, 59, 7625-7634.
74. Dive, V.; Lucet-Levannier, K.; Georgiadis, D.; Cotton, J.; Vassiliou, S. et al. Phosphinic peptide inhibitors as tools in the study of the function of zinc metallopeptidases. Biochem. Soc. Trans. 2000, 28, 455-460.
75. Chen, H.; Roques, B. P.; Fournie-Zaluski, M. C. Design of the first highly potent and selective aminopeptidase N (EC 3.4.11.2) inhibitor. Bioorg. Med. Chem. Lett. 1999, 9, 1511-1516.
76. Thunnissen, M. M. G. M.; Nordlund, P.; Haeggstrom, J. Z. Crystal structure of human leukotriene A4 hydrolase, a bifunctional enzyme in inflammation. Nat. Struct. Biol. 2001, 8, 131-135.
77. Oleksyszyn, J.; Subotkowska, L.; Mastalerz, P. Diphenyl 1-aminoalkanephosphonates. Synthesis 1979, 985-986.
78. Szewczyk, J.; Lejczak, B.; Kafarski, P. Transesterification of diphenyl phosphonates using the pottasium fluoride/crown ether/alcohol system; Part1. Transesterification of diphenyl 1-(benzyloxycarbonylamino)-alkanephosphonates. Synthesis 1982, 409-412.
79. Bartlett, P. A.; Hanson, J. E.; Giannousis, P. P. Potent inhibition of pepsin and penicillopepsin by phosphorus-containing peptide analogues. J. Org. Chem. 1990, 55, 6268-6274.
80. Kozlowski, J. K.; Rath, N. P.; Spilling, C. D. Determination of the enantiomeric purity and absolute configuration of a-hydroxy phosphonates. Tetrahedron 1995, 51, 6385-6396.
81. Stetter, H.; Kuhlmann, H. Eine einfache herstellung von α-alkylacrylsaure-estern. Synthesis 1979, 29-30.
82. Meltzer, R. I.; Lustgarten, D. M.; Fischman, A. Thyroxine analogues. J. Org. Chem. 1957, 22, 1577-1581.
83. Insight 97 Molecular Modelling Program Package; 97.0 ed.; Molecular Simulations Inc.: San Diego.
84. Ligand_Design 97 Molecular Modelling Program Package; 97.0 ed.; Molecular Simulations Inc.: San Diego.
85. Discover, Molecular Modelling Program Package; 97.0 ed.; Molecular Simulation: San Diego.
86. Strater, N.; Lipscomb, W. N.; Klabunde, T.; Krebs, B. Two - metal ions catalysis in enzymatic acyl- and phosphoryl-transfer reactions. Angew. Chem., Int. Ed. 1996, 35, 2024-2055.
87. Bohm, H. J.; Klebe, G. What can we learn from molecular recognition in protein-ligand complexes for the design of new drugs? Angew. Chem., Int. Ed. Engl. 1996, 35, 2588-2614.
88. Altschul, S. F.; Gish, W.; Miller, W.; Myers, E. W.; Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 1990, 215, 403-410.
89. Altschul, S. F.; Madden, T. L.; Schaffer, A. A.; Zhang, J.; Zhang, Z. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25, 3389-3402.
90. Higgins, D.; Thompson, J.; Gibson, T.; Thompson, J. D.; Higgins, D. G. et al. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22, 4673-4680.
91. Sali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 1993, 234, 779-815.