The 10th and 11th residues of parathyroid hormone PTH(1-12) analogues were substituted to study the structure and function of PTH analogues. The substitution of Ala10 of [Ala3,10,12(Leu 7/Phe7)Arg11]rPTH(1-12)NH2 with Glu10 and/or the Arg11 with Ile11 markedly decreased cAMP generating activity. Data from circular dichroism (CD) and the nuclear magnetic resonance (NMIR) structural analysis of [Ala 3,10,12(Leu7/ Phe7)Arg11]rPTH(1-12) NH2 revealed tight α-helical structures, while the Glu 10 and/or Ile11 substituted analogues showed unstable α-helical structures. We conclude that 10th and 11th residues are important for stabilizing its helical conformation and that destabilization of the α-helical structure, induced by substituting the above residues, remarkably affect its biological potency.
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