The 10th and 11th residues of short length N-terminal PTH(1-12) analogue are important for its optimum potency

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Abstract

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.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalJournal of Peptide Research
Volume64
Issue number1
DOIs
Publication statusPublished - 2004 Jul 1

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Circular Dichroism
Parathyroid Hormone
Structural analysis
Conformations
Substitution reactions
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
amino-terminal parathyroid hormone

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

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title = "The 10th and 11th residues of short length N-terminal PTH(1-12) analogue are important for its optimum potency",
abstract = "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.",
author = "Lim, {S. K.} and Lee, {E. J.} and Kim, {H. Y.} and W. Lee",
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T1 - The 10th and 11th residues of short length N-terminal PTH(1-12) analogue are important for its optimum potency

AU - Lim, S. K.

AU - Lee, E. J.

AU - Kim, H. Y.

AU - Lee, W.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - 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.

AB - 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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