Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?
文献类型：期刊论文
| 作者 | Yang, Yang2; Xu, Zhijian1,2 ; Zhang, Zhengyan2,4; Yang, Zhuo2; Liu, Yingtao2; Wang, Jinan2; Cai, Tingting2; Li, Shujin4; Chen, Kaixian2; Shi, Jiye3
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| 刊名 | JOURNAL OF PHYSICAL CHEMISTRY B
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| 出版日期 | 2015-09-10 |
| 卷号 | 119期号:36页码:11988-11997 |
| ISSN号 | 1520-6106 |
| DOI | 10.1021/acs.jpcb.5b04130 |
| 文献子类 | Article |
| 英文摘要 | A database survey in this study revealed for the first time that there are 227 counterintuitive like-charge guanidinium pairings (Gdm(+) -Arg pairings) between ligands and receptors in the Protein Data Bank, implying the potential guanidinium arginine binding between guanidine-containing drugs and their target proteins. Furthermore, there are 145 guanidine-containing molecules in the DrugBank, showing the prevalence of guanidinium groups in drugs. It has also been reported that the introduction of a guanidinium group forming Gdm(+) -Arg pairing improved the potency of the drug by more than 8-fold in a typical case. On the basis of the survey, six ligand-protein complexes with typical Gdm(+) -Arg pairings were chosen for QM/MM calculations. The calculations at the B97-D/6-311++g(d,p) level revealed that the interaction could be as strong as -1.0 to -2.5 kcal/mol in DMSO and water, comparable to common intermolecular interactions. The calculations also unveiled that the Gdm(+) -Arg pairing interactions change from repulsive to attractive with the increase of dielectric constant, suggesting that the dielectric constant has a general stabilization effect on the Gdm(+) -Arg pairing. This study suggested that the like-charge guanidinium pairing interaction could be used not only for tuning the physical and chemical properties of drug leads but also for improving ligand binding affinity. |
| WOS关键词 | HUMAN PARAINFLUENZA VIRUS ; AMBER FORCE-FIELD ; NEURAMINIDASE INHIBITORS ; HEMAGGLUTININ-NEURAMINIDASE ; BIOLOGICAL-ACTIVITIES ; MOLECULAR-DYNAMICS ; ION-PAIR ; WATER ; INFLUENZA ; PROTEINS |
| 资助项目 | National Natural Science Foundation of China[81273435] ; National Natural Science Foundation of China[81302699] ; National High Technology Research and Development Program of China[2012AA01A305] ; National Science & Technology Major Project[2013ZX09103001-001] ; National Science & Technology Major Project[2012ZX09301001-004] ; China Postdoctoral Science Foundation[2014T70444] ; State Key Laboratory of Medicinal Chemical Biology, Nankai University[20130265] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000361254200003 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276399]  |
| 专题 | 药物发现与设计中心 上海药物代谢研究中心 |
| 通讯作者 | Xu, Zhijian |
| 作者单位 | 1.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.UCB Pharma, Dept Informat, Slough SL1 4EN, Berks, England; 4.Soochow Univ, Coll Chem Chem Engn & Mat Sci, Suzhou 215123, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Yang,Xu, Zhijian,Zhang, Zhengyan,et al. Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2015,119(36):11988-11997. |
| APA | Yang, Yang.,Xu, Zhijian.,Zhang, Zhengyan.,Yang, Zhuo.,Liu, Yingtao.,...&Zhu, Weiliang.(2015).Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?.JOURNAL OF PHYSICAL CHEMISTRY B,119(36),11988-11997. |
| MLA | Yang, Yang,et al."Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?".JOURNAL OF PHYSICAL CHEMISTRY B 119.36(2015):11988-11997. |
入库方式： OAI收割
来源：上海药物研究所
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