Volume 5, Issue 3, September 2019, Page: 33-39
New ACE Inhibitor Designed from Nicotianamine and Its Docking Pose Prediction Using the Gold Program
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
Received: Jul. 16, 2019;       Accepted: Aug. 7, 2019;       Published: Aug. 23, 2019
DOI: 10.11648/j.jddmc.20190503.11      View  628      Downloads  210
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.
Nicotianamine, Structure-Activity-Relationship Study, Angiotensin I-Converting Enzyme Inhibitors, Molecular Docking Study, Allosteric Binding Site
To cite this article
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, Journal of Drug Design and Medicinal Chemistry. Vol. 5, No. 3, 2019, pp. 33-39. doi: 10.11648/j.jddmc.20190503.11
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