An approach to the elucidation of metabolic breakdown products of the luteinizing hormone-releasing hormone.
Metabolic breakdown of the luteinizing hormone-releasing hormone (LH-RH) could lead to the following fragments containing pyroglutamic acid: pyroglutamic acid (1), pGlu-His (2), pGLu-His-Trp (3), pGlu-His-Trp-Ser (4), etc., and finally pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly (10). We have synthesized fragments 2-10 and successfully separated all ten metabolites and LH-RH by high-performance liquid chromatography (HPLC) with a muBondapak C18 column. In a test of the viability of the method, cochromatography of fragments 1-10 and LH-RH with the products of chymotryptic digestion of tritiated LH-RH showed radioactive peaks corresponding to the expected products, fragments 3 and 5. Analysis of the products of incubation of a rat kidney homogenate supernatant with LH-RH showed fragments 1-4 and LH-RH. The finding of breakdown at position 4 uncovers a new site of LH-RH breakdown and points the way to the design of potential LH-RH antagonists and agonists where the 4 position would be substituted with unnatural amino acids to prevent breakdown.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000138:chemical synthesis / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism; D051381:Rats
D010446:Peptide Fragments; D007987:Gonadotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid