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Molecular Pharmacology

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Research ArticleArticle

Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective Binding of a Potent Enantiomeric Inhibitor

Manna Huang, Yongxian Shao, Jianying Hou, Wenjun Cui, Beibei Liang, Yingchun Huang, Zhe Li, Yinuo Wu, Xinhai Zhu, Peiqing Liu, Yiqian Wan, Hengming Ke and Hai-Bin Luo
Molecular Pharmacology November 2015, 88 (5) 836-845; DOI: https://doi.org/10.1124/mol.115.099747
Manna Huang
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Yongxian Shao
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Jianying Hou
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Wenjun Cui
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Beibei Liang
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Yingchun Huang
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Zhe Li
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Yinuo Wu
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Xinhai Zhu
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Peiqing Liu
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Yiqian Wan
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Hengming Ke
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Hai-Bin Luo
School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
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Article Information

vol. 88 no. 5 836-845
DOI 
https://doi.org/10.1124/mol.115.099747
PubMed 
26316540

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0026-895X
Online ISSN 
1521-0111
History 
  • Received May 7, 2015
  • Accepted August 24, 2015
  • Published online September 30, 2015.

Article Versions

  • Earlier version (August 27, 2015 - 09:37).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Manna Huang,
  2. Yongxian Shao,
  3. Jianying Hou,
  4. Wenjun Cui,
  5. Beibei Liang,
  6. Yingchun Huang,
  7. Zhe Li,
  8. Yinuo Wu,
  9. Xinhai Zhu,
  10. Peiqing Liu,
  11. Yiqian Wan,
  12. Hengming Ke, and
  13. Hai-Bin Luo
  1. School of Chemistry and Chemical Engineering (M.H., J.H., X.Z. Yiq.W.), School of Pharmaceutical Sciences (Y.S., Z.L., Yin.W., P.L., H.-B.L.), Sun Yat-Sen University, Guangzhou, PR China; and Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (W.C., B.L., Y.H., H.K.)
  1. Address correspondence to:
    Dr. Hengming Ke, University of North Carolina, 120 Mason Farm Road, Chapel Hill, NC 27599. E-mail: hke{at}med.unc.edu or Dr. Hai-Bin Luo, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China. E-mail: luohb77{at}mail.sysu.edu.cn or Dr. Yiqian Wan, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China. E-mail: ceswyq{at}mail.sysu.edu.cn
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Molecular Pharmacology: 88 (5)
Molecular Pharmacology
Vol. 88, Issue 5
1 Nov 2015
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Research ArticleArticle

Asymmetric Recognition of PDE9 Inhibitors

Manna Huang, Yongxian Shao, Jianying Hou, Wenjun Cui, Beibei Liang, Yingchun Huang, Zhe Li, Yinuo Wu, Xinhai Zhu, Peiqing Liu, Yiqian Wan, Hengming Ke and Hai-Bin Luo
Molecular Pharmacology November 1, 2015, 88 (5) 836-845; DOI: https://doi.org/10.1124/mol.115.099747

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Research ArticleArticle

Asymmetric Recognition of PDE9 Inhibitors

Manna Huang, Yongxian Shao, Jianying Hou, Wenjun Cui, Beibei Liang, Yingchun Huang, Zhe Li, Yinuo Wu, Xinhai Zhu, Peiqing Liu, Yiqian Wan, Hengming Ke and Hai-Bin Luo
Molecular Pharmacology November 1, 2015, 88 (5) 836-845; DOI: https://doi.org/10.1124/mol.115.099747
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