Antibody catalyzed cleavage of an amide bond using an external nucleophilic cofactor

Journal of the American Chemical Society

Volumn 120, Issue 4, 1998, Pages 817-818

  Ersoy, Oguz ^a,b   Fleck, Roman ^a   Sinskey, Anthony ^a   Masamune, Satoru ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; CATALYTIC ANTIBODY; HAPTEN; HYDROLASE;

ANTIBODY COMBINING SITE; ANTIGEN BINDING; ARTICLE; CATALYSIS; CATALYST; CHEMISTRY; CONTROLLED STUDY; DRUG SYNTHESIS; HYDROLYSIS; NONHUMAN;

EID: 0032481331     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9732542     Document Type: Article

References (34)

1. For recent reviews on catalytic antibodies, see: (a) Lerner, R. A.; Benkovic, S. J.; Schultz, P. G. Science 1991, 252, 659. (b) Schultz, P. G.; Lerner, R. A. Acc. Chem Res. 1993, 26, 391. (c) Schultz, P. G.; Lerner, R. A. Science 1995, 269, 1835. (d) MacBeath, G.; Hilvert, D. Chem. Biol. 1996, 3 (6), 433.
2. For recent reviews on catalytic antibodies, see: (a) Lerner, R. A.; Benkovic, S. J.; Schultz, P. G. Science 1991, 252, 659. (b) Schultz, P. G.; Lerner, R. A. Acc. Chem Res. 1993, 26, 391. (c) Schultz, P. G.; Lerner, R. A. Science 1995, 269, 1835. (d) MacBeath, G.; Hilvert, D. Chem. Biol. 1996, 3 (6), 433.
3. For recent reviews on catalytic antibodies, see: (a) Lerner, R. A.; Benkovic, S. J.; Schultz, P. G. Science 1991, 252, 659. (b) Schultz, P. G.; Lerner, R. A. Acc. Chem Res. 1993, 26, 391. (c) Schultz, P. G.; Lerner, R. A. Science 1995, 269, 1835. (d) MacBeath, G.; Hilvert, D. Chem. Biol. 1996, 3 (6), 433.
4. For recent reviews on catalytic antibodies, see: (a) Lerner, R. A.; Benkovic, S. J.; Schultz, P. G. Science 1991, 252, 659. (b) Schultz, P. G.; Lerner, R. A. Acc. Chem Res. 1993, 26, 391. (c) Schultz, P. G.; Lerner, R. A. Science 1995, 269, 1835. (d) MacBeath, G.; Hilvert, D. Chem. Biol. 1996, 3 (6), 433.
5. (a) For an encouraging early effort, see: Janda, K. D.; Schloeder, D.; Benkovic, S. J.; Lerner, R. A. Science 1988, 241, 1188.
6. For other efforts toward amide hydrolysis, see: (a) Pollack, S. J.; Hsiun, P.; Schultz, P. G. J. Am. Chem. Soc. 1989, 111, 5961. (b) Iverson, B. L.; Lerner, R. A. Science 1989, 243, 1184. (c) Gibbs, R. A.; Tayler, S.; Benkovic, S. J. Science 1992, 258, 803. (d) Liotta, L. J.; Benkovic, P. A.; Miller, G. P.; Benkovic, S. J. J. Am. Chem. Soc. 1993, 115, 350. (e) Martin, M. T.; Angeles, T. S.; Sugasawara, R.; Aman, N. I.; Napper, A. D.; Darsley, M. J.; Sanchez, R. I.; Booth, P.; Titmas, R. C. J. Am. Chem. Soc. 1994, 116, 6508.
7. For other efforts toward amide hydrolysis, see: (a) Pollack, S. J.; Hsiun, P.; Schultz, P. G. J. Am. Chem. Soc. 1989, 111, 5961. (b) Iverson, B. L.; Lerner, R. A. Science 1989, 243, 1184. (c) Gibbs, R. A.; Tayler, S.; Benkovic, S. J. Science 1992, 258, 803. (d) Liotta, L. J.; Benkovic, P. A.; Miller, G. P.; Benkovic, S. J. J. Am. Chem. Soc. 1993, 115, 350. (e) Martin, M. T.; Angeles, T. S.; Sugasawara, R.; Aman, N. I.; Napper, A. D.; Darsley, M. J.; Sanchez, R. I.; Booth, P.; Titmas, R. C. J. Am. Chem. Soc. 1994, 116, 6508.
8. For other efforts toward amide hydrolysis, see: (a) Pollack, S. J.; Hsiun, P.; Schultz, P. G. J. Am. Chem. Soc. 1989, 111, 5961. (b) Iverson, B. L.; Lerner, R. A. Science 1989, 243, 1184. (c) Gibbs, R. A.; Tayler, S.; Benkovic, S. J. Science 1992, 258, 803. (d) Liotta, L. J.; Benkovic, P. A.; Miller, G. P.; Benkovic, S. J. J. Am. Chem. Soc. 1993, 115, 350. (e) Martin, M. T.; Angeles, T. S.; Sugasawara, R.; Aman, N. I.; Napper, A. D.; Darsley, M. J.; Sanchez, R. I.; Booth, P.; Titmas, R. C. J. Am. Chem. Soc. 1994, 116, 6508.
9. For other efforts toward amide hydrolysis, see: (a) Pollack, S. J.; Hsiun, P.; Schultz, P. G. J. Am. Chem. Soc. 1989, 111, 5961. (b) Iverson, B. L.; Lerner, R. A. Science 1989, 243, 1184. (c) Gibbs, R. A.; Tayler, S.; Benkovic, S. J. Science 1992, 258, 803. (d) Liotta, L. J.; Benkovic, P. A.; Miller, G. P.; Benkovic, S. J. J. Am. Chem. Soc. 1993, 115, 350. (e) Martin, M. T.; Angeles, T. S.; Sugasawara, R.; Aman, N. I.; Napper, A. D.; Darsley, M. J.; Sanchez, R. I.; Booth, P.; Titmas, R. C. J. Am. Chem. Soc. 1994, 116, 6508.
10. For other efforts toward amide hydrolysis, see: (a) Pollack, S. J.; Hsiun, P.; Schultz, P. G. J. Am. Chem. Soc. 1989, 111, 5961. (b) Iverson, B. L.; Lerner, R. A. Science 1989, 243, 1184. (c) Gibbs, R. A.; Tayler, S.; Benkovic, S. J. Science 1992, 258, 803. (d) Liotta, L. J.; Benkovic, P. A.; Miller, G. P.; Benkovic, S. J. J. Am. Chem. Soc. 1993, 115, 350. (e) Martin, M. T.; Angeles, T. S.; Sugasawara, R.; Aman, N. I.; Napper, A. D.; Darsley, M. J.; Sanchez, R. I.; Booth, P.; Titmas, R. C. J. Am. Chem. Soc. 1994, 116, 6508.
11. (a) Suga, H.; Ersoy, O.; Tsumuraya, T.; Lee, J.; Sinskey, A. J.; Masamune, S. J. Am. Chem. Soc. 1994, 116, 487.
12. (b) Suga, H.; Ersoy, O.; Williams, S. F.; Tsumuraya, T.; Margolies, M. N.; Sinskey, A. J.; Masamune, S. J. Am. Chem. Soc. 1994, 116, 6025.
13. (c) Tsumuraya, T.; Suga, H.; Meguro, S.; Tsukanawa, A.; Masamune, S. J. Am. Chem. Soc. 1995, 117, 11390.
14. (a) Carter P.; Wells, J. A. Nature 1988, 332, 564.
15. (b) Fink, A. L.; Enzyme Mechanisms; Page, M. I., Williams, A., Eds.; The Royal Society of Chemistry; London, 1987; p 159.
16. (a) Baldwin, E.; Schultz, P. G. Science 1989, 245, 1104.
17. (b) For a novel protocol to elicit reactive residues in antibody binding sites by "Reactive Immunization", see: Wagner, J.; Lerner, R. A.; Carlos, F. B. Science 1995, 270, 1797.
18. Ersoy, O.; Fleck, R.; Sinskey, A. J.; Masamune, S. J. Am. Chem. Soc. 1996, 118, 13077.
19. The underlying genetic principles of heterologous immunization are currently under investigation in our laboratories and will be published in due course.
20. (a) Goding, J. Monoclonal Antibodies: Principles and Practice, 2nd ed.; Academic Press: New York, 1986.
21. (b) Harlow, E.; Lane, D. Antibodies. A Laboratory Manual; Cold Spring Harbor Labratory: New York, 1988.
22. (a) Janda, K. D.; Shevlin, C. G.; Lerner, R. A. Science 1993, 259, 490.
23. (b) Janda, K. D.; Shevlin, C. G.; Lerner, R. A. J. Am. Chem. Soc. 1995, 117, 2659.
24. (c) Na, J.; Houk, K. N.; Shevlin, C. G.; Janda, K. D.; Lerner, R. A. J. Am. Chem. Soc. 1993, 115, 8453.
25. (d) Shabat, D.; Itzhaky, H.; Reymond, J.-L.; Keinan, E. Nature 1995, 374, 143.
26. (e) Schultz, P. G.; Lerner, R. A. Acc. Chem. Res. 1993, 26, 391.
27. a difference (greater than 6 units) beween the phenol and nitroaniline. The antibodies are capable of rerouting this process in favor of nitroanilide expulsion.
28. There could be steric repulsion between the o-hydrogen of phenol and the β-hydrogens of propionamide 1 since the hapten structure represents this as a carbon-carbon bond. As a result, phenol and amide 1 might not assume an optimal orientation within the antibody in terms of the phenol attack angle, phenol deprotonation, and anilide protonation. However, it seems that antibodies do provide some flexibility in accommodating different substrates.
29. (a) Angeles, T. S.; Smith, R. G.; Darsley, M. J.; Sugasawara, R.; Sanchez, R. I.; Kenten, J.; Schultz, P. G.; Martin, M. T. Biochemistry 1993, 32, 12128.
30. (b) Martin, M. T. Drug Discovery Today 1996, 1 (6), 239.
31. (a) Suga, H.; Tanimoto, N.; Sinskey, A. J.; Masamune, S. J. Am. Chem. Soc. 1994, 116, 11197.
32. (b) Yu, J.; Hsieh, L. C.; Kochersperger, L.; Yonkovich, S.; Stephans, J. C.; Gallop, M. A.; Schultz, P. G. Angew. Chem., Int. Ed. Engl. 1994, 33, 339.
33. (c) Reymond, J.-L.; Janda, K. D.; Lerner, R. A. Angew. Chem., Int. Ed. Engl. 1991, 30, 1711.
34. (d) Scanlan, T. S.; Prudent, J. R.; Schultz, P. G. J. Am. Chem. Soc. 1991, 113, 9397.