Modification of the proline residue of TRH enhances biological activity and inhibits degradation.
An analogue of TRH with a modified proline residue (Pyr-His-MepNH2) has been synthesised and evaluated. In CNS, but not endocrine tests the analogue had improved activity compared to TRH and was more resistant to enzymatic degradation. A metabolite of TRH, His-Pro, was without biological activity. It is concluded that the biological actions attributed to TRH are due to the parent tripeptide rather than His-Pro and that these actions can be enhanced by improving the biological stability of TRH.
D000818:Animals; D001711:Biotransformation; D001831:Body Temperature / Q000187:drug effects; D004355:Drug Stability; D008297:Male; D051379:Mice; D011388:Prolactin / Q000097:blood; D011392:Proline; D012110:Reserpine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine; D011388:Prolactin; D011392:Proline