The structure and function of short-length amino terminal PTH analogues were studied. The substitution of Leu7 with Phe in [Ala3,10Leu7 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 [Ala3,10 Leu7 Arg11]rPTH(1-11)NH2 caused nearly a complete loss of cAMP formation. Meanwhile, NMR analysis of [(Ala1/Ser1)Ala3,10 (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.
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