Isotopically sensitive regioselectivity in the oxidative deamination of a homologous series of diamines catalyzed by diamine oxidase.
The equivalence of aminomethylene groups in selected diamine substrates of diamine oxidase was exploited for the determination of intramolecular isotope effects. In the series of substrates, [1,1-2H2]-1,3-diaminopropane, [1,1-2H2]-1,5-diaminopentane, [1,1-2H2]-1,6-diaminohexane, [1,1-2H2]-1,7-diaminoheptane and [alpha,alpha-2H2]-4-(aminomethyl)benzylamine, the preference of the enzyme for reaction at the unlabeled methylene was found to vary from 1.45 to 10.5-fold. The observed partitioning ratios go through a minimum value with 1,5-diaminopentane, the best substrate of diamine oxidase of the compounds tested. The results suggest that fast substrates have less opportunity to reorient into alternate binding conformations while bound to the active site of the enzyme. On the other hand, diamine substrates tested that cannot exist in energetically favorable conformations with internitrogen distances of about 7-8 A showed larger intramolecular isotope effects.
Callery
P S
PS
Department of Biomedicinal Chemistry, University of Maryland, Baltimore 21201.
Subramanyam
B
B
Yuan
Z M
ZM
Pou
S
S
Geelhaar
L A
LA
Reynolds
K A
KA
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003903:Deuterium; D003959:Diamines / Q000737:chemistry / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013379:Substrate Specificity; D013552:Swine
D003959:Diamines; D003903:Deuterium; D006631:Amine Oxidase (Copper-Containing)