AMINOALKYLAZIRIDINES AS SUBSTRATES AND INHIBITORS OF LYSYL OXIDASE: SPECIFIC INACTIVATION OF THE ENZYME BY N-(5-AMINOPENTYL)AZIRIDINE

Narasimhan Nagan¹, Patrick S. Callery² and Herbert M. Kagan¹

1 Department of Biochemistry, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, and the ² Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506

Received 4/2/98 Accepted4/6/98

7. REFERENCES

1. H. M. Kagan: Characterization and regulation of lysyl oxidase. In: Biology of the extracellular matrix, Vol l: Regulation of matrix accumulation. Ed: Mecham R P, Academic Press, Orlando (1986)

2. R. C. Siegel: Lysyl oxidase. Int Rev Connect Tiss Res 8, 73-118 (1979)

3. S. X. Wang, M. Mure, K. F. Medzihradszky, A. L. Burlingame, D. Brown, D. M. Dooley, A. J. Smith, H. M. Kagan & J. P. Klinman: A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains. Science 273, 1078-84 (1996)

4. S. N. Gacheru, P. C. Trackman, S. D. Calaman, F. T. Greenaway & H. M. Kagan: Vicinal diamines as PQQ-directed, irreversible inhibitors of lysyl oxidase. J Biol Chem 264, 12963-12969 (1989)

5. S. S. Tang, P. C. Trackman & H. M. Kagan: Reaction of aortic lysyl oxidase with ß-aminopropionitrile. J Biol Chem 258, 4331-4338 (1983)

6. S. S. Tang, D. E. Simpson & H. M. Kagan: ß-Substituted ethylamine derivatives as suicide inhibitors of lysyl oxidase. J Biol Chem 259, 975-979 (1984)

7. S. S. Tang, C. O. Chichester & H. M. Kagan: Comparative sensitivities of purified preparations of lysyl oxidase and other amine oxidases to active site-directed enzyme inhibitors. Conn Tissue Res 19, 93-103 (1989)

8. P. R. Williamson & H. M. Kagan: Electronegativity of aromatic amines as a basis for the development of ground state inhibitors of lysyl oxidase. J Biol Chem 262, 14520-14524 (1987)

9. J. W. Conner, Z. M. Yuan & P. S. Callery: Active-site directed irreversible inhibition of diamine oxidase by a homologous series of aziridinylalkylamines. Biochem Pharmacol 44, 1229-1232 (1992)

10. V. Steinebach, B. W. Groen, S. S. Wijmenga, W. M. A. Niessen, J. A. Jongejan & Duine, J. A.: Identification of topaquinone, as illustrated for pig kidney diamine oxidase and Escherichia coli amine oxidase. Anal Biochem 230, 159-166 (1995)

11. S. M. Janes, M. M. Palcic, C. H. Scaman, A. J. Smith, D. E. Brown, D. M. Dooley, M. Mure & J. P. Klinman: Identification of topaquinone and its consensus sequence in copper amine oxidases. Biochemistry 31, 12147-12154 (1992)

12. J. E. Earley, C. E. O’Rourke, L. B. Clapp, J. O. Edwards &B. C. Lawes: Reaction of ethyleneimines. IX. The mechanisms of ring openings of ethyenimines in acidic aqueous solutions. J Am Chem Soc 80, 3458-3462 (1958)

13. Y. Yamada, T. Imoto & S. Noshita: Modification of catalytic groups in lysozyme. Biochemistry 21, 2187-2192 (1982)

14. C. Weise, H.-J. Kreienkamp, R. Raba, A. Pedak, A. Aaviksaar & F. Hucho: Anionic sites of the acetylcholinesterase from Torpedo californica: affinity labelling with the cationic reagent N,N-dimethyl-2-phenylaziridinium. EMBO J 9, 3885-3888 (1990)

15. A. Sepp & J. Järv: Alkylation of acetylcholinesterase anionic center with aziridinium ion accelerates the enzyme acylation step. Biochim Biophys Acta 1077, 407-412 (1991)

16. H. M. Kagan & P. Cai: Isolation of active site peptides of lysyl oxidase. Meth Enzymol 258, 122-132 (1995)

17. U. K. Laemmli: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685 (1970)

18. K. A. Sullivan & H. M. Kagan: Evidence for structural similarities in the multiple forms of aortic and cartilage lysyl oxidase and a catalytically quiescent aortic protein. J Biol Chem 257, 13520-13526 (1982)

19. H. M. Kagan, K. A. Sullivan, T. A. Olsson & A. L. Cronlund: Purification and properties of four species of lysyl oxidase from bovine aorta. Biochem J 177, 203-214 (1979)

20. Y. Li, A. D. MacKerell, M. J. Egorin, M. F. Ballesteros, D. M. Rosen, Y.-Y. Wu, D. A. Blamble & P. S. Callery, P: Comparative molecular field analysis-based predictive model of structure-function relationships of polyamine transport inhibitors in L1210 cells. Canc. Res. 57, 234-239 (1997)

21. Y.-Y. Wu: Synthesis and evaluation of aziridine-containing compounds as inhibitors of porcine kidney diamine oxidase (Thesis). Baltimore, MD: University of Maryland (1994).

22. H. M. Kagan & K. A. Sullivan: Lysyl oxidase: preparation and role in elastin biosynthesis. Meth Enzymol 82, 637-649 (1982)

23. P. C. Trackman, C. G. Zoski & H. M. Kagan: Development of a peroxidase-coupled fluorometric assay for lysyl oxidase. Anal Biochem 113, 336-342 (1981)

24. R. Kitz & I. B. Wilson: Esters of methanesulfonic acid as irreversible inhibitors of acetylcholine esterase. J Biol Chem 237, 3245-3249 (1962)

25. H. M. Kagan. & P. C. Trackman: Lysyl oxidase. In: Principles and applications of quinoproteins. Ed: Davidson V, Marcel Dekker, NY (1993)

26. H. M. Kagan, M. A. Williams, P. R. Williamson & J. M. Anderson: Influence of sequence and charge on the specificity of lysyl oxidase toward protein and synthetic peptide substrates. J. Biol. Chem. 259, 11203-11207 (1984)