Synthesis, Molecular Modelling and Biological Evaluation of Protectin D1 and Analogs

Recently it was reported that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are oxidized to potent signal molecules such as protectin D1, which halts inflammation processes with high in vivo potency. In this project derivatives of protectin D1 will be synthesized and subjected to biological testing and molecular modeling studies.

Structure of the polyunsaturated compound Protectin D1.

The numerous and variable processes of inflammation resolution are governed by interacting programs of chemical mediators. In the cases where leukocyte apoptosis is present, inflammation resolution is executed by clearance of dead cells by phagocytes.Today resolution is considered to be a distinct process from anti-inflammatory processes. The resolution of inflammation is accompanied by an active switch in the mediators that predominate in exudates.

Initially, mediators, such as prostaglandins and leukotrienes, which activate and amplify the important signs of inflammation, are generated.

Next, prostaglandin E2 and prostaglandin D2, by inducing the production of key enzymes, gradually promote the synthesis of mediators that have both anti-inflammatory and proresolution activities, such as the lipoxins, resolvins and protectins.

Protectins are the coined term for a series of DHA derived mediators characterized by the presence of a conjugated triene double bond structure and 22 carbons with an additional three double bonds. The stereochemistry of the common triene moiety and the stereochemistry of the additional three double bonds give rise to the different protectins.

 

Published Feb. 15, 2011 9:54 PM - Last modified May 13, 2011 11:52 AM