Specificity in the enzymic conversion of substituted cis‐8, cis‐11, cis‐14‐eicosatrienoic acids into prostaglandins

Abstract

The enzyme specificity in the biosynthesis of prostaglandins has been investigated by incubation of a particulate fraction of sheep vesicular glands with substituted cis-8,cis-11 ,cis-14eicosatrienoic acids. Conversions were always lower than with the unsubstituted acid (20 : 3). In the 2-substituted series, a conversion of up to 50% was found for 2-methoxycarbonyl-; 2-methyl-; 2-hydroxymethyl-; 2-butyl-; 2-methoxy-; 2-methoxymethylene-; 2-fluoro-; 2-bromo-; 2-cyano-; and 2-phenyl-20: 3. No conversion was found for 2-hydroxycarbonyl-; 2-heptoxycarbonyl-; 2-amino-; and 2-acetamido-20:3. In some cases, a slight preference of the enzymes for the R configuration (2-phenyL; 2-methyl-20 : 3) was noted. For di-substituted acids, yields of up to 70% were found for 2-cyano-2-butyL; 2,3-cis-and 2,3-transmethylene-; 3,3-dimethyl-20 : 3, but 4,4-dimethyl-20 : 3 was not converted. However, 5-yne-20 : 3 was again a substrate (25% conversion). Substitution at the methyl end of the precursor acid resulted in 34% conversion with 19-methyl-20: 3, but 18-methyl-20 : 3 was not converted. Biological activities of substituted prostaglandins were, in general, much less than those of PGE,, but for 1Pmethyl-PGE,, smooth muscle-stimulating activity was 1.6 times that of PGE,. For some substituted prostaglandins (2-fluoro-; 2-cyano-PGE1), an appreciable activity in one biological test system was found but very little in others.Biochim. Biophys. Acta 90, 204 (1964). ' S. Berystrom, H . Danielsson and B. Samuelsson, Biochim. Biophys. Acta 90, 207 (1964).