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

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‐14‐eicosatrienoic 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‐trans‐methylene‐ ; 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 PGE1, but for 19‐methyl‐PGE1, smooth muscle‐stimulating activity was 1.6 times that of PGE1. For some substituted prostaglandins (2‐fluoro‐ ; 2‐cyano‐PGE1), an appreciable activity in one biological test system was found but very little in others.