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 language | English |
|---|---|
| Pages (from-to) | 25-32 |
| Number of pages | 8 |
| Journal | Journal of Peptide Research |
| Volume | 64 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2004 Jul 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Endocrinology
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The 10th and 11th residues of short length N-terminal PTH(1-12) analogue are important for its optimum potency. / Lim, S. K.; Lee, E. J.; Kim, H. Y.; Lee, W.
In: Journal of Peptide Research, Vol. 64, No. 1, 01.07.2004, p. 25-32.Research output: Contribution to journal › Article
TY - JOUR
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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UR - http://www.scopus.com/inward/citedby.url?scp=3142757090&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3011.2004.00163.x
DO - 10.1111/j.1399-3011.2004.00163.x
M3 - Article
C2 - 15200475
AN - SCOPUS:3142757090
VL - 64
SP - 25
EP - 32
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 1
ER -