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Global Minimum Energy Conformations of Thyrotropin Releasing Hormone Analogs by Simulated Annealing.II a
Ramón Garduño-Juárez & Faustino Pérez-Neri
b
a
Instituto de Fisica Universidad Nacional Autonoma de México , Apdo. Postal 139-B, 62191 , Cuernavaca , Morelos , México b
Facultad de Ciencias Quimicas e Industriales , Universidad Autonoma del Edo. de Morelos , Cuernavaca , Morelos , México Published online: 21 May 2012.
To cite this article: Ramón Garduño-Juárez & Faustino Pérez-Neri (1991) Global Minimum Energy Conformations of Thyrotropin Releasing Hormone Analogs by Simulated Annealing.II, Journal of Biomolecular Structure and Dynamics, 8:4, 737-758, DOI: 10.1080/07391102.1991.10507842 To link to this article: http://dx.doi.org/10.1080/07391102.1991.10507842
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or
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Downloaded by [New York University] at 12:38 13 January 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions
Journal of Biomolecular Structure & Dynamics, /SSN 0739-1102 Volume 8, Issue Number 4 (1991), "'Adenine Press (1991).
Global Minimum Energy Conformations of Thyrotropin Releasing Hormone Analogs by Simulated Annealing.II ' G ard uno- Juarez ' h , ...-v·aus t'tno P'erez- N en' 2 R amon Downloaded by [New York University] at 12:38 13 January 2015
1
Instituto de Fisica Universidad Nacional Autonoma de Mexico Apdo. Postal139-B, 62191 Cuernavaca, Morelos. Mexico 2
Facultad de Ciencias Quimicas e Industriales Universidad Autonoma del Edo. de Morelos Cuernavaca, Morelos. Mexico
Abstract Lowest conformational energy structures of seventeen thyrotropin releasing hormone analogs have been studied by simulated annealing. A surprising conformational similarity was observed for the peptide backbone. The possible role of each substituent in its biological activity is inferred. A composite hydrogen-bonding environment is proposed for the TRH with respect to receptor binding.
Introduction The use of simulated annealing as an algorithm that enables us to find the known global minimum energy conformations of small peptides (1) has shown its effectiveness. We have already employed simulated annealing to find good local minima of Thyrotropin Releasing Hormone (TRH) analogs with heterocyclic substituents replacing the ring system of p-Glu, which have known crystal structure and biological activity (1 ). Now, in this paper we report minimum energy conformations of seventeen other TRH analogs with modifications in the histidine, proline and carboxamide functions, for which there is information on their biological activity (2). See Chart I. Many structure-function relationship studies on TRH analogs have been performed in order to better understand the mechanisms of its hormonal activity (2,3). These studies have indicated that the entire molecule is required for its full biological activity; however, the necessity of each functional group is not yet clear. TRH has been proposed as a neurotransmitter or a neuromodulator since it has been found *Author to whom correspondence should be addressed.
737
738
Garduno·Juarez & Perez·Neri Chart I Relative Potencies of TRH Analogs with Several Modifications, After Vale eta/. (2) TRH analog
% TRH potency
pGlu-His-Pro-NH 2
100%
pGlu-R-Pro-NH 2 I
II III IV
Downloaded by [New York University] at 12:38 13 January 2015
v VI VII VIII IX
R R R R R R R R R
=-Met = -Tyr= -Arg= -Orn= -Lys= -Gly= [3-Met-His 2) = [l-Met-His2) = (pyrazolyl-3)-Ala
1.0 % 0.08 0.05 0.02 0.02 0.005 800.0 0.04 5.0
pGlu-His-R-NH 2 X XI XII XIII
R R R R
= -HyPro=-Leu= -Gly= -Trp-
0.14% 0.04
Journal of Biomolecular Structure and Dynamics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tbsd20
Global Minimum Energy Conformations of Thyrotropin Releasing Hormone Analogs by Simulated Annealing.II a
Ramón Garduño-Juárez & Faustino Pérez-Neri
b
a
Instituto de Fisica Universidad Nacional Autonoma de México , Apdo. Postal 139-B, 62191 , Cuernavaca , Morelos , México b
Facultad de Ciencias Quimicas e Industriales , Universidad Autonoma del Edo. de Morelos , Cuernavaca , Morelos , México Published online: 21 May 2012.
To cite this article: Ramón Garduño-Juárez & Faustino Pérez-Neri (1991) Global Minimum Energy Conformations of Thyrotropin Releasing Hormone Analogs by Simulated Annealing.II, Journal of Biomolecular Structure and Dynamics, 8:4, 737-758, DOI: 10.1080/07391102.1991.10507842 To link to this article: http://dx.doi.org/10.1080/07391102.1991.10507842
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [New York University] at 12:38 13 January 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions
Journal of Biomolecular Structure & Dynamics, /SSN 0739-1102 Volume 8, Issue Number 4 (1991), "'Adenine Press (1991).
Global Minimum Energy Conformations of Thyrotropin Releasing Hormone Analogs by Simulated Annealing.II ' G ard uno- Juarez ' h , ...-v·aus t'tno P'erez- N en' 2 R amon Downloaded by [New York University] at 12:38 13 January 2015
1
Instituto de Fisica Universidad Nacional Autonoma de Mexico Apdo. Postal139-B, 62191 Cuernavaca, Morelos. Mexico 2
Facultad de Ciencias Quimicas e Industriales Universidad Autonoma del Edo. de Morelos Cuernavaca, Morelos. Mexico
Abstract Lowest conformational energy structures of seventeen thyrotropin releasing hormone analogs have been studied by simulated annealing. A surprising conformational similarity was observed for the peptide backbone. The possible role of each substituent in its biological activity is inferred. A composite hydrogen-bonding environment is proposed for the TRH with respect to receptor binding.
Introduction The use of simulated annealing as an algorithm that enables us to find the known global minimum energy conformations of small peptides (1) has shown its effectiveness. We have already employed simulated annealing to find good local minima of Thyrotropin Releasing Hormone (TRH) analogs with heterocyclic substituents replacing the ring system of p-Glu, which have known crystal structure and biological activity (1 ). Now, in this paper we report minimum energy conformations of seventeen other TRH analogs with modifications in the histidine, proline and carboxamide functions, for which there is information on their biological activity (2). See Chart I. Many structure-function relationship studies on TRH analogs have been performed in order to better understand the mechanisms of its hormonal activity (2,3). These studies have indicated that the entire molecule is required for its full biological activity; however, the necessity of each functional group is not yet clear. TRH has been proposed as a neurotransmitter or a neuromodulator since it has been found *Author to whom correspondence should be addressed.
737
738
Garduno·Juarez & Perez·Neri Chart I Relative Potencies of TRH Analogs with Several Modifications, After Vale eta/. (2) TRH analog
% TRH potency
pGlu-His-Pro-NH 2
100%
pGlu-R-Pro-NH 2 I
II III IV
Downloaded by [New York University] at 12:38 13 January 2015
v VI VII VIII IX
R R R R R R R R R
=-Met = -Tyr= -Arg= -Orn= -Lys= -Gly= [3-Met-His 2) = [l-Met-His2) = (pyrazolyl-3)-Ala
1.0 % 0.08 0.05 0.02 0.02 0.005 800.0 0.04 5.0
pGlu-His-R-NH 2 X XI XII XIII
R R R R
= -HyPro=-Leu= -Gly= -Trp-
0.14% 0.04
