Electronegativity of aromatic amines as a basis for the development of ground state inhibitors of lysyl oxidase
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'-/sup 2/H)benzylamines. In contrast, there was no Dkcat solvent isotope effect with (/sup 2/H) H/sub 2/O 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 the retardation of substrate oxidation by electronegative substituents. Such ground state stabilization can result in compounds with increased potential for the inhibition of the oxidation of protein substrates of lysyl oxidase.
- Research Organization:
- Boston Univ. School of Medicine, MA
- OSTI ID:
- 5670030
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 262:30
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINES
STRUCTURE-ACTIVITY RELATIONSHIPS
DEUTERIUM
ISOTOPE EFFECTS
OXIDOREDUCTASES
ENZYME INHIBITORS
ELECTRONS
PYRIDINES
REDOX REACTIONS
SUBSTRATES
TRACER TECHNIQUES
AZINES
CHEMICAL REACTIONS
ELEMENTARY PARTICLES
ENZYMES
FERMIONS
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEPTONS
LIGHT NUCLEI
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
STABLE ISOTOPES
550201* - Biochemistry- Tracer Techniques