Sulfonyl Esters Research Articles

Studies on phospholipase a and its zymogen from porcine pancreas IV. The influence of chemical modification of the lecithin structure on substrate properties

1.1. A series of chemically modified lecithins were used to investigate by kinetic analyses their substrate c.q. inhibitor properties for porcine pancreatic phospholipase A. The substrate analogues used were systematically modified in: the stereochemical configuration, the susceptible ester bond, the phosphate moiety, the alkylchains, the glycerol backbone and in the position of the phosphorylcholine moiety.2.2. The desired relationship between chemical structure and inhibitory properties requires elimination of purely physical effects of the inhibitor on the organization of the substrate molecules at the lipid-water interface.3.3. Lecithins of the opposite stereochemical configuration and certain lecithin analogues with a modification of the susceptible ester bond were found to be purely competitive inhibitors. The 1-sn-phosphatidylcholines have Ki values identical to the K8 values of the corresponding 3-sn-phosphatidylcholines. The lecithin analogues with an acylamide linkage at the 2-position were found to be the most potent competitive inhibitors, while on the contrary substitution of the acylester bond by a sulfonyl ester linkage does not give rise to inhibitory properties.4.4. Lecithins with a modification in the glycerol-phosphate bond and in the position of the phosphorylcholine moiety are substrates, but exhibit much lower V values and their binding constants are similar to those of the corresponding normal substrates.5.5. Introduction of two methyl groups at the carbon atom adjacent to the carboxyl in the acyl chain of the potentially susceptible ester bond gives a lecithin which is not degraded by the enzyme. The presence of only one methyl branch in this position greatly diminishes the hydrolysis rate, probably due to steric hindrance.6.6. Increasing the distance between the susceptible ester bond and the phosphate moiety in a lecithin by introducing a methylene group completely abolishes enzymatic activity. These lecithin analogues were found to be competitive inhibitors.7.7. The minimal requirements for a phospholipid to be a substrate for phospholipase A, as established earlier, should be extended to include the fact that the phosphate moiety can be replaced by a phosphonate or sulfonate group.

Conversion of Cellobiose into Lactose

Benzyl 2, 3, 6-tri-O-acetyl-4-O-(2,3-di-O-acetyl-4,6-di-O-methylsulfonyl-β-d-glucopyranosyl)-β-d-glucopyranoside (VI) was prepared from α-cellobiose octaacetate. Displacement of the sulfonyl esters of VI with acyloxy-groups in N, N-dimethyl formamide in the presence of sodium benzoate gave 4-O-β-d-galactopyranosyl-d-glucopyranose derivative (lactose derivative). Elimination of blocking groups of the derivative yielded lactose hydrate (IX), though the overall yield of lactose from cellobiose octaacetate was less than 2%.