Year: 2026
Type: article
Abstract: Mechanistic studies have yielded novel prostaglandin analogs and acyclic products initially of interest in understanding cyclooxygenase (COX) structure and function, later found in vivo and of interest because of unique biological activities. Beyond arachidonic acid, fatty acid substrates span from 18 to 22 carbons and may contain ester/amide modification or epoxide/hydroxy moieties at the first double bond. Stereocontrol with the unconventional substrates remains largely intact although cyclization may be diverted or halted altogether, and catalysis proceeds with the insertion of one, two, or three molecules of oxygen into substrates. A switch in stereochemistry at the 15-carbon occurs in a natural COX from coral and has received attention upon aspirin treatment of COX-2. The latter produces 15R-hydroxyeicosatetraenoic acid and analogs from other fatty acids that may be further oxygenated by lipoxygenases. Functional plasticity in COX catalysis has enabled the formation and discovery of a host of novel eicosanoids and provided mechanistic insight into the COX reaction mechanisms.
Source: Journal of Biological Chemistry
Authors: Claus Schneider, Alan R. Brash
Institution: Vanderbilt University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,430
Awards: G2354238959, G2380919889
OpenAlex ID: W7127629187