New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program

Noboru Takada; Takaharu Okada; Eri Kogawa; Yohsuke Sanada; Ayumi Ishidoya

doi:doi:10.11648/j.jddmc.20190503.11

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New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program

Noboru Takada, Takaharu Okada, Eri Kogawa, Yohsuke Sanada, Ayumi Ishidoya

Published in Journal of Drug Design and Medicinal Chemistry (Volume 5, Issue 3)

Received: 16 July 2019 Accepted: 7 August 2019 Published: 23 August 2019

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Abstract

Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.

Published in	Journal of Drug Design and Medicinal Chemistry (Volume 5, Issue 3)
DOI	10.11648/j.jddmc.20190503.11
Page(s)	33-39
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Nicotianamine, Structure-Activity-Relationship Study, Angiotensin I-Converting Enzyme Inhibitors, Molecular Docking Study, Allosteric Binding Site

References

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APA Style

Noboru Takada, Takaharu Okada, Eri Kogawa, Yohsuke Sanada, Ayumi Ishidoya. (2019). New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program. Journal of Drug Design and Medicinal Chemistry, 5(3), 33-39. https://doi.org/10.11648/j.jddmc.20190503.11

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ACS Style

Noboru Takada; Takaharu Okada; Eri Kogawa; Yohsuke Sanada; Ayumi Ishidoya. New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program. J. Drug Des. Med. Chem. 2019, 5(3), 33-39. doi: 10.11648/j.jddmc.20190503.11

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AMA Style

Noboru Takada, Takaharu Okada, Eri Kogawa, Yohsuke Sanada, Ayumi Ishidoya. New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program. J Drug Des Med Chem. 2019;5(3):33-39. doi: 10.11648/j.jddmc.20190503.11

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@article{10.11648/j.jddmc.20190503.11,
  author = {Noboru Takada and Takaharu Okada and Eri Kogawa and Yohsuke Sanada and Ayumi Ishidoya},
  title = {New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {5},
  number = {3},
  pages = {33-39},
  doi = {10.11648/j.jddmc.20190503.11},
  url = {https://doi.org/10.11648/j.jddmc.20190503.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20190503.11},
  abstract = {Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.},
 year = {2019}
}

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TY  - JOUR
T1  - New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program
AU  - Noboru Takada
AU  - Takaharu Okada
AU  - Eri Kogawa
AU  - Yohsuke Sanada
AU  - Ayumi Ishidoya
Y1  - 2019/08/23
PY  - 2019
N1  - https://doi.org/10.11648/j.jddmc.20190503.11
DO  - 10.11648/j.jddmc.20190503.11
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 33
EP  - 39
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20190503.11
AB  - Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.
VL  - 5
IS  - 3
ER  -

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Author Information

Noboru Takada

Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan
Takaharu Okada

Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan
Eri Kogawa

Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan
Yohsuke Sanada

Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan
Ayumi Ishidoya

Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan

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APA Style

Noboru Takada, Takaharu Okada, Eri Kogawa, Yohsuke Sanada, Ayumi Ishidoya. (2019). New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program. Journal of Drug Design and Medicinal Chemistry, 5(3), 33-39. https://doi.org/10.11648/j.jddmc.20190503.11

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ACS Style

Noboru Takada; Takaharu Okada; Eri Kogawa; Yohsuke Sanada; Ayumi Ishidoya. New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program. J. Drug Des. Med. Chem. 2019, 5(3), 33-39. doi: 10.11648/j.jddmc.20190503.11

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AMA Style

Noboru Takada, Takaharu Okada, Eri Kogawa, Yohsuke Sanada, Ayumi Ishidoya. New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program. J Drug Des Med Chem. 2019;5(3):33-39. doi: 10.11648/j.jddmc.20190503.11

Copy | Download

@article{10.11648/j.jddmc.20190503.11,
  author = {Noboru Takada and Takaharu Okada and Eri Kogawa and Yohsuke Sanada and Ayumi Ishidoya},
  title = {New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {5},
  number = {3},
  pages = {33-39},
  doi = {10.11648/j.jddmc.20190503.11},
  url = {https://doi.org/10.11648/j.jddmc.20190503.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20190503.11},
  abstract = {Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program
AU  - Noboru Takada
AU  - Takaharu Okada
AU  - Eri Kogawa
AU  - Yohsuke Sanada
AU  - Ayumi Ishidoya
Y1  - 2019/08/23
PY  - 2019
N1  - https://doi.org/10.11648/j.jddmc.20190503.11
DO  - 10.11648/j.jddmc.20190503.11
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 33
EP  - 39
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20190503.11
AB  - Hypertension is currently one of the most serious health issues worldwide. Nicotianamine, a non-peptide-type amino acid trimer, is ubiquitously present in higher plants and plays a role as an internal metal transporter. It is known that nicotianamine inhibits ACE activity and that oral treatment with the compound improves hypertension. However the mode of action remains unclear, due to lack of crystallographic data. Although a structure-activity relationship study of nicotianamine has the potential to uncover the details of the inhibition profile, the azetidine-2-carboxylic acid moiety in nicotianamine has become a critical barrier for further biochemical research due to limited commercial supply and difficulties with structural modification. In this paper, ten nicotianamine analogs without azetidine-2-carboxylic acid moiety were prepared and their inhibition of angiotensin I-converting enzyme was investigated. Among these analogs, a phenylalanine analog, (2S,3′S,3″S)-N-{3′-(3″-amino-3″-carboxypropylamino)-3′-carboxypropyl}phenylalanine, displayed the most potent activity. The inhibition activity of the compound corresponded to that of captopril. These results suggested a possibility of structural modification of nicotianamie to develop antihypertensive drugs. Molecular docking studies with Gold were also performed to predict the binding poses of nicotianamine and its analog, suggesting that nicotianamine and its analogs combine a plausible allosteric site in an area away from the catalytic site in ACE.
VL  - 5
IS  - 3
ER  -

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