INTERACTION OF ORGANOPHOSPHORUS ANALOGS OF AMINO-ACIDS WITH P450

1. This study deals with the oxidation of organophosphorus amino acid analogues by phenobarbital-induced rabbit liver microsomes. It has bee n shown that 1-aminoalkyphosphonous and 1-aminoalkylthiophosphonic aci ds are converted by P450 to 1-aminoalkylphosphonic acids. 2. Phosphono us analogues of amino acids cause type I spectral changes, and thiopho sphonic analogues produce reverse type I changes in difference spectra . 3. In the presence of NADPH, the 1-aminoalkylphosphonous acids form the corresponding 1-aminoalkylphosphonic acids by the reaction P-H --> P-OH, as monitored using H-1 nmr spectroscopy. 4. Aminoalkylthiophosp honic acids have also proven to be the substrates for the NADPH-depend ent monoxygenase system. During the course of oxidative desulphuration 1-aminoalkylphosphonic acids were formed by the reaction P=S --> P=O, as monitored by P-31-nmr spectroscopy. 5. Using resonance Raman (RR) spectroscopy, the interaction of 1-aminoisobutylphosphonous acid with P450 was investigated, and characteristic changes in spectral frequenc ies in the region between 1370 and 1700 cm(-1) were demonstrated. Thes e latter changes indicate that substrate binding of organophosphorus c ompounds leads to alterations in haem conformation and to redistributi on of the electron density.