Brown_1987_Environ.Health.Perspect_72_5

In addition to their use in the polyurethane and pesticide industries, isocyanates have proven to be useful probes for the exploration of protein structure. This paper focuses on three aspects of isocyanates: their broad reactivity, their reversible interaction with cholinesterases, and the relative hydrolysis rates of alkyl and aryl isocyanates. The broad reactivity of isocyanates as well as the demonstrated affinity labeling of serine and sulfhydryl esterases are discussed. Extension of the affinity labeling studies to include the analysis of the inhibition of cholinesterases by methyl isocyanate shows that methyl isocyanate is not an effective inhibitor of any of the cholinesterases. The inhibition of cholinesterases by alkyl isocyanates shows a pattern of decreased specificity with decreased alkyl chain length. The inhibition of cholinesterases by isocyanates is shown to be reversible, with a maximum rate of reversal seen at physiological pH. This reversal is characteristic of the reaction of an isocyanate with a sulfhydryl group. Finally, the affinity labeling of proteins must compete successfully with the hydrolysis of isocyanates in aqueous solution. The hydrolysis of alkyl isocyanates is shown to be significantly slower than that of the aryl isocyanates.