HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Williamson, P. R. Articles by Kagan, H. M. Search for Related Content PubMed PubMed Citation Articles by Williamson, P. R. Articles by Kagan, H. M. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 262, Issue 30, 14520-14524, Oct, 1987

Electronegativity of aromatic amines as a basis for the development of ground state inhibitors of lysyl oxidase

PR Williamson and HM Kagan
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.

Benzylamine derivatives containing para substituents of differing electronegativity as well as isomers of aminomethylpyridine have been assessed for their substrate and inhibitor potentials toward lysyl oxidase. Substituted benzylamines with increasingly electronegative para substituents had the lowest KI values and thus were the most effective inhibitors of the oxidation of elastin by lysyl oxidase. The kcat values for these compounds as substrates of lysyl oxidase were also reduced with increasingly electronegative para substituents. Both the Dkcat and D(kcat/Km) kinetic isotope effects decreased with increasingly electronegative p-substituents in [alpha, alpha'- 2H]benzylamines. In contrast, there was no Dkcat solvent isotope effect with [2H] H2O while the D(kcat/Km) solvent isotope effect tended to increase with increasingly electronegative p-substituents. These results are consistent with the stabilization of an enzyme-generated substrate carbanion and thus the retardation of substrate oxidation by electronegative substituents. Such ground state stabilization thus can result in compounds with increased potential for the inhibition of the oxidation of protein substrates of lysyl oxidase.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Liu, K. Nellaiappan, and H. M. Kagan Irreversible Inhibition of Lysyl Oxidase by Homocysteine Thiolactone and Its Selenium and Oxygen Analogues. IMPLICATIONS FOR HOMOCYSTINURIA J. Biol. Chem., December 19, 1997; 272(51): 32370 - 32377. [Abstract] [Full Text] [PDF]