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

S. K. Lim; E. J. Lee; H. Y. Kim; W. Lee

doi:10.1111/j.1399-3011.2004.00163.x

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

S. K. Lim, E. J. Lee, H. Y. Kim, W. Lee

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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 [Ala^3,10,12(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 language	English
Pages (from-to)	25-32
Number of pages	8
Journal	Journal of Peptide Research
Volume	64
Issue number	1
DOIs	https://doi.org/10.1111/j.1399-3011.2004.00163.x
Publication status	Published - 2004 Jul

All Science Journal Classification (ASJC) codes

Biochemistry
Endocrinology

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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",

year = "2004",

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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

Y1 - 2004/7

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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