Effect of obligatory replacement and conformational restriction on psychotropic activity of thyroliberin analogs

Article abstract of DOI:10.1007/bf02494506

Easy lactamization of Gln(Asn)-Pro-NH₂ with the formation of cyclic dipeptides with the diketopiperazine structure (mimetics of the conformational fragments of linear tripeptides with the X-Pro trans-bond) was observed in the synthesis of tripeptide Glp-Gln-Pro-NH₂ modified by the replacement of histidinc with obligatory similar glutamine in thyroliberin (Glp-His-Pro-NH₂, TRH) and in the synthesis of its structural analog [Asn²]TRH. Ion peaks corresponding to the Glp and Pro amino acid residues were revealed in the mass spectra of the peptides synthesized. The biological properties of the compounds obtained were determined indicating that the obligatory replacement resulted in an increased physiological specificity of [Gln²]TRH. The enhanced activity of conformationally restricted cyclic peptides compared to linear ones suggests that the biologically active conformation responsible for the antidepressant activity of linear TRH analogs is the conformation with X-Pro trans-bond.