[Frontiers in Bioscience 3, a23-26, May 1, 1998]

	[Frontiers in Bioscience 3, a23-26, May 1, 1998] Reprints PubMed CAVEAT LECTOR
	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 1. ABSTRACT The reaction of lysyl oxidase was assessed with members of a series of aminoalkylaziridines in which the primary amino group and the aziridinyl nitrogen were separated by 3-7 methylene carbons. Among these, N-(5-aminopentyl)aziridine proved to be the poorest substrate by far and to inhibit the enzyme activity. Aminoalkylaziridines with chain lengths shorter or longer than five carbons did not inhibit the enzyme. The resulting inhibition was competitive with productive substrates and became irreversible with time, following pseudo first order kinetics with a K_I of 0.22 mM. N-(5-aminopentyl)aziridine appears to act as a bifunctional affinity label covalently interacting with the active site of this enzyme.

[Frontiers in Bioscience 3, a23-26, May 1, 1998]
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PubMed
CAVEAT LECTOR

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

1. ABSTRACT

The reaction of lysyl oxidase was assessed with members of a series of aminoalkylaziridines in which the primary amino group and the aziridinyl nitrogen were separated by 3-7 methylene carbons. Among these, N-(5-aminopentyl)aziridine proved to be the poorest substrate by far and to inhibit the enzyme activity. Aminoalkylaziridines with chain lengths shorter or longer than five carbons did not inhibit the enzyme. The resulting inhibition was competitive with productive substrates and became irreversible with time, following pseudo first order kinetics with a K_I of 0.22 mM. N-(5-aminopentyl)aziridine appears to act as a bifunctional affinity label covalently interacting with the active site of this enzyme.