Structure and function of a minimal receptor activation domain of parathyroid hormone

The structure and function of short-length amino terminal PTH analogues were studied. The substitution of Leu⁷ with Phe in [Ala^3,10Leu⁷ Arg¹¹]rPTH(1-11 NH₂ analogue peptides did not show any reduction in cAMP formation. Replacement of the 1st, 7th and 8th residues revealed different activities, depending upon the residue type. The substitution of Ala¹ by Ser in [Ala^3,10 Leu⁷ Arg¹¹]rPTH(1-11)NH₂ caused nearly a complete loss of cAMP formation. Meanwhile, NMR analysis of [(Ala¹/Ser¹)Ala^3,10 (Leu⁷/Phe⁷)Arg¹¹]rPTH(1-11 NH₂ revealed an α-helical backbone structure with a flexible conformation at the carboxyl-terminus. The overall results suggest that 11-residue short oligopeptide analogues of PTH tend to form an α-helical structure and the different activities of those analogues could be associated with residue specificity rather than the secondary conformational structure.