Lipase active-site-directed anchoring of organometallics: Metallopincer/protein hybrids

Chemistry - A European Journal

Volumn 11, Issue 23, 2005, Pages 6869-6877

  Kruithof, Cornells A ^a   Casado, Miguel A ^a   Guillena, Gabriela ^a   Egmond, Maarten R ^b   Van Der Kerk van Hoof, Anca ^b   Heck, Albert J R ^b   Gebbink, Robertas J M Klein ^a   Van Koten, Gerard ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Inhibitors; Lipases; Metallopincer complexes; Organometallic phosphonate; Protein modifications

Indexed keywords

LIPASES; METAL COMPLEXES; METAL LEACHING;

COMPLEXATION; MASS SPECTROMETRY; PROTEINS; TRANSITION METALS;

ORGANOMETALLICS;

ORGANOMETALLIC COMPOUND; TRIACYLGLYCEROL LIPASE;

BINDING SITE; CHEMISTRY; CONFERENCE PAPER; ELECTROSPRAY MASS SPECTROMETRY; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; ULTRAVIOLET SPECTROPHOTOMETRY;

BINDING SITES; LIPASE; MAGNETIC RESONANCE SPECTROSCOPY; ORGANOMETALLIC COMPOUNDS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SPECTROPHOTOMETRY, ULTRAVIOLET;

EID: 27944457200     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200500671     Document Type: Conference Paper

References (66)

1. a) D. Qi, C.-M. Tann, D. Haring, M. D. Distefano, Chem. Rev. 2001, 101, 3081-3111, and references therein;
2. b) J. Rademann, Angew. Chem. 2004, 116, 4654-4656;
3. Angew. Chem. Int. Ed. 2004, 43, 4554-4556;
4. c) G. DeSantis, J. B. Jones, Curr. Opin. Biotechnol. 1999, 10, 324-330.
5. E. T. Kaiser, D. S. Lawrence, Science 1984, 226, 505-511.
6. M. E. Wilson, G. M. Whitesides, J. Am. Chem. Soc. 1978, 100, 306-307.
7. a) C.-C. Lin, C.-W. Lin, A. S. C. Chan, Tetrahedron: Asymmetry 1999, 10, 1887-1893;
8. b) M. T. Reetz, Tetrahedron 2002, 55, 6595-6602;
9. c) M. T. Reetz, Angew. Chem. 2001, 113, 292-320;
10. Angew. Chem. Int. Ed. 2001, 40, 284-310;
11. d) M. T. Reetz, M. Rentzsch, A. Pletsch, M. Maywald, Chimia 2002, 56, 721-723;
12. e) J. Collot, J. Gradinaru, N. Humbert, M. Skander, A. Zocchi, T. R. Ward, J. Am. Chem. Soc. 2003, 125, 9030;
13. f) M. Ohashi, T. Koshiyame, T. Ueno, M. Yanase, H. Fujii, Y. Watanabe, Angew. Chem. 2003, 115, 1035-1038;
14. Angew. Chem. Int. Ed. 2003, 42, 1005-1008;
15. g) G. Guillena, C. A. Kruithof, M. A. Casado, M. R. Egmond, G. van Koten, J. Organomet. Chem. 2003, 668, 3-7;
16. h) J. R. Carey, S. K. Ma, T. D. Pfister, D. K. Garner, H. K. Kim, J. A. Abramite, Z. Wang, Z. Guo, Y. Lu, J. Am. Chem. Soc. 2004, 126, 10812-10813;
17. i) H. Sato, T. Hayashi, T. Ando, Y. Hisaeda, T. Ueno, Y. Watanabe, J. Am. Chem. Soc. 2004, 126, 436-437;
18. j) C. M. Thomas, T. R. Ward, Chem. Soc. Rev. 2005, 34, 337-346, and references therein;
19. k) C. Letondor, N. Humbert, T. R. Ward, Proc. Nat. Acad. Sci. USA 2005, 101, 4683-4687;
20. l) T. Ueno, T. Koshiyama, M. Ohashi, K. Kondo, M. Kono, A. Suzuki, T. Yamane, Y. Watanabe, J. Am. Chem. Soc. 2005, 127, 6556-6562;
21. m) Y. Lu, Curr. Opin. Chem. Bio. 2005, 9, 118-126;
22. n) Y. Watanabe, Curr. Opin. Chem. Bio. 2005, 6, 208-216.
23. a) A. Hoepping, M. Reisgys, P. Brust, S. Seifert, H. Spies, R. Alberto, B. Johannsen, J. Med. Chem. 1998, 41, 4429-4432;
24. b) R. S. Pandurangi, K. V. Katti, L. Stillwell, C. L. Barnes, J. Am. Chem. Soc. 1998, 120, 1134-11373;
25. c) M. Salmain, G. Jaouen, C. R. Chimie 2003, 6, 249-258.
26. a) I. W. McNae, K. Fishburn, A. Habtemariam, T. M. Hunter, M. Melchart, F. Wang. M. D. Walkinshaw, P. J. Sadler, Chem. Commun. 2004, 1786-1787;
27. b) T. Hayashi, Y. Hisaeda, Acc. Chem. Res. 2002, 35, 35-43;
28. c) M. Salmain, A. Gorfti, G. Jaouen, Eur. J. Biochem. 1998, 255, 192-199.
29. A. Fenselau, D. Koenig, D.E. Koshland Jr., H. G. Latham Jr., H. Weiner, Proc. Nat. Acad. Sci USA 1967, 57, 1670-1675.
30. C. A. Kruithof, G. Guillena, M. R. Egmond, G. van Koten, Book of Abstracts, First International Symposium on Bioorganometallic Chemistry, 18-20 July 2002, Paris, p. 104.
31. a) F. Björkling, A. Dahl, S. Patkar, M. Zundel, Bioorg. Med. Chem. 1994, 2, 697-705;
32. b) J. C. Powers, J. L. Asgian, Ö. D. Ekici, K.E. James, Chem. Rev. 2002, 102, 4639-4750;
33. c) N. Jessani, J. A. Young, S. L. Diaz, M. P. Patricelli, A. Varki, B. F. Cravatt, Angew. Chem. 2005, 117, 2452-2455;
34. Angew. Chem. Int. Ed. 2005, 44, 2400-2403.
35. a) C. D. Hodneland, Y.-S. Lee, D.-H. Min, M. MrKsich, Proc. Natl. Acad. Sci. USA 2002, 99, 5048-5052;
36. b) G. Zandonella, P. Stadler, L. Haalck, F. Spener, F. Paltauf, A. Hermetter, Eur. J. Biochem. 1999, 262, 63-69.
37. So far, no experimental details concerning the formation of such a metal complex have been presented, see reference [4d].
38. P. E. Kolattukudy, Lipases, Elsevier, Amsterdam, 1984, pp. 471-501.
39. C. Martinez, P. Geus, M. Lauwereys, M. Matthyssens, C. Cambillau, Nature 1992, 356, 615-618.
40. M. Albrecht, G. van Koten, Angew. Chem. 2001, 113, 3866-3898;
41. Angew. Chem. Int. Ed. 2001, 40, 5000-5031.
42. a) M. Albrecht, M. Lutz, A. L. Spek, G. van Koten, Nature 2000, 406, 970-974;
43. b) G. Guillena, K. M. Kalkes, G. Rodríguez, G. D. Batema, G. van Koten, J. P. Kamerling, Org. Lett. 2003, 5, 2021-2024;
44. c) D. Becatti, K. M. Kalkes, G. Guillena, A. Carvalho de Souza, G. van Koten, J. P. Kamerling, ChemBioChem 2005, 6, 1196-1203.
45. a) J. T. Singleton, Tetrahedron 2003, 59, 1837-1857;
46. b) H. P. Dijkstra, M. Q. Slagt, A. McDonald, C. A. Kruithof, R. Kreiter, A. M. Mills, M. Lutz, A. L. Spek, W. Klopper, G. P. M. van Klink, G. van Koten, Eur. J. Inorg. Chem. 2003, 830-838;
47. c) H. P. Dijkstra, C. A. Kruithof, N. Ronde, R. van de Coevering, D. J. Ramón, D. Vogt, G. P. M. van Klink, G. van Koten, J. Org. Chem. 2003, 68, 675-685.
48. M. Q. Slagt, G. Rodriguez, M. P. Grutters, R. J. M. Klein Gebbink, W. Klopper, L. W. Jenneskens, M. Lutz, A. L. Spek, G. van Koten, Chem. Eur. J. 2004, 10, 1331-1344.
49. The space-filling representations were derived from a crystal structure of wild-type cutinase inhibited by ethylhexyl phosphonate-p-nitrophenyl ester (obtained from http://www.rcsb.org/pdb/, PDB ID: 1XZL, published in reference [25 b]) and from crystal structures of the corresponding pincer metal complexes (NCNPtCl, corresponding to ASCD 1, is taken from M. Albrecht, M. Lutz, A. M. M. Schreurs, E. T. H. Lutz, A. L. Spek, G. van Koten J. Chem. Soc. Dalton Trans. 2000, 3797; SCS complexes corresponding to ASCD 2 and 3: from unpublished results). The pincer units were attached to the propyl chain of the inhibitor after removal of one methyl and 2 methylene groups from the hexyl chain. The complexes were connected by chemically justified angles (sp3 bonds) and orientated by best fit into the protein in such a manner, that no conformational changes of cutinase were necessary and no atom overlap occurred. No further alterations were made to the structure. The pictures were generated using Spartan and Molekel software packages. No geometry optimization calculations were performed. Due to the absence of a "lid" covering the active site of cutinase, the active site is freely accessible and therefore such a modification of the protein does not have a large effect on its overall structure. Because an inhibited crystal structure is used, without changes of any atom coordinates, the resulted representations give a good indication of the overall structure of the hybrids. It is important to note is that we have also used ASCDs without a thether; that is, the aromatic ring is directly connected to the phosphorous atom and as a result, the metal is burried deeper into the active site of cutinase. In this position the complex experiences more steric hindrance by the lipase, according to a representation of the hybrid obtained as indicated above. Interestingly, the hybrid formation rate is indeed a factor of 360 slower. This result also indicates that the choice of tether length can be estimated according to these representations of the hybrids. In conclusion, the space-filling representations give an indication of the overall structure, the approximate distance of the metal center from the phosphorous atom and whether a designed ASCDs would fit or not.
50. For synthesis and analytical data see the Supporting Information.
51. a) A. Suzuki, J. Organomet. Chem. 1999, 576, 147-168;
52. b) I. Pergament, M. Srebnik, Org. Lett. 2001, 5, 217-219.
53. a) C. P. Jongh, A. Zwierzak, T. A. Modro, Phosphorus Sulfur Silicon Relat. Elem. 1991, 61, 205-209;
54. b) A. Koziara, A. Zwierzak Tetrahedron 1976, 32, 1649-1654.
55. a) B. R. Steele, K. Vrieze, Trans. Met. Chem. 1977, 2, 140-144;
56. b) A. Canty, J. Patel, B. W skelton, A. H. White, J. Organomet. Chem. 2000, 599, 195-199.
57. D. M. Grove, G. van Koten, J. N. Louwen, L. G. Noltes, A. L. Spek, H. J. C. J. Ubbels, J. Am. Chem. Soc. 1982, 104, 6609-6616.
58. The molar extinction coefficient of p-nitrophenolate was determined using p-nitrophenol in the same buffer as during the incubation experiments of cutinase by the ASDCs.
59. a) M. L. M. Mannesse, G. H. de Haas, H. T. W. M. van der Heijden, M. R. Egmond, H. M. Verheij, Biochem. Soc. Trans. 1997, 25, 165-170;
60. b) S. Longhi, M. L. M. Mannesse, H. M. Verheij, G. H. de Haas, M. R. Egmond, E. Knoop-Mouthuy, C. Cambillau, Protein Science 1997, 6, 275-286;
61. c) J.-F. Cavalier, G. Buono, Acc. Chem. Res. 2000, 33, 579-588.
62. The reference cuvet contained the reagents in the same concentrations except for the presence of cutinase. Because in this case the reference cuvet was prepared first, a small amount of 2 was dissolved before the reaction mixture was measured, causing the actual negative absorption at the beginning of the reaction.
63. Dialysis was performed using a membrane cassette (Slide-A-Lyzer 10 K) with a 10 kDa cut-off mass purchased from Pierce Biotechnology (http://www.piercenet.com/).
64. ESI-MS spectra are presented in the Supporting Information.
65. S. Komiya, Synthesis of Organometallic Compounds, Wiley, Chichester, 1997.
66. G. Rodríguez, M. Albrecht, J. Schoenmaker, A. Ford, M. Lutz, A. L. Spek, G. van Koten, J. Am. Chem. Soc. 2002, 124, 5127-5138.