schliessen

Filtern

 

Bibliotheken

Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?

A database survey in this study revealed for the first time that there are 227 counterintuitive like-charge guanidinium pairings (Gdm super(+)-Arg pairings) between ligands and receptors in the Protein Data Bank, implying the potential guanidinium-arginine binding between guanidine-containing drugs... Full description

Journal Title: The journal of physical chemistry. B September 10, 2015, Vol.119(36), pp.11988-11997
Main Author: Yang, Yang
Other Authors: Xu, Zhijian , Zhang, Zhengyan , Yang, Zhuo , Liu, Yingtao , Wang, Jinan , Cai, Tingting , Li, Shujin , Chen, Kaixian , Shi, Jiye , Zhu, Weiliang
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1520-5207 ; DOI: 10.1021/acs.jpcb.5b04130
Link: http://search.proquest.com/docview/1711537970/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1711537970
title: Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?
format: Article
creator:
  • Yang, Yang
  • Xu, Zhijian
  • Zhang, Zhengyan
  • Yang, Zhuo
  • Liu, Yingtao
  • Wang, Jinan
  • Cai, Tingting
  • Li, Shujin
  • Chen, Kaixian
  • Shi, Jiye
  • Zhu, Weiliang
subjects:
  • Arginine–Metabolism
  • Databases, Protein–Chemistry
  • Drug Design–Metabolism
  • Electrons–Pharmacology
  • Guanidine–Chemistry
  • Ligands–Metabolism
  • Models, Molecular–Metabolism
  • Protein Conformation–Metabolism
  • Proteins–Metabolism
  • Thermodynamics–Metabolism
  • Ligands
  • Proteins
  • Arginine
  • Guanidine
ispartof: The journal of physical chemistry. B, September 10, 2015, Vol.119(36), pp.11988-11997
description: A database survey in this study revealed for the first time that there are 227 counterintuitive like-charge guanidinium pairings (Gdm super(+)-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 super(+)-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 super(+)-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 super(+)-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 super(+)-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.
language: eng
source:
identifier: E-ISSN: 1520-5207 ; DOI: 10.1021/acs.jpcb.5b04130
fulltext: fulltext
issn:
  • 15205207
  • 1520-5207
url: Link


@attributes
ID314776573
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1711537970
sourceidproquest
recordidTN_proquest1711537970
sourcesystemPC
pqid1711537970
display
typearticle
titleLike-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?
creatorYang, Yang ; Xu, Zhijian ; Zhang, Zhengyan ; Yang, Zhuo ; Liu, Yingtao ; Wang, Jinan ; Cai, Tingting ; Li, Shujin ; Chen, Kaixian ; Shi, Jiye ; Zhu, Weiliang
contributorYang, Yang (correspondence author) ; Yang, Yang (record owner)
ispartofThe journal of physical chemistry. B, September 10, 2015, Vol.119(36), pp.11988-11997
identifierE-ISSN: 1520-5207 ; DOI: 10.1021/acs.jpcb.5b04130
subjectArginine–Metabolism ; Databases, Protein–Chemistry ; Drug Design–Metabolism ; Electrons–Pharmacology ; Guanidine–Chemistry ; Ligands–Metabolism ; Models, Molecular–Metabolism ; Protein Conformation–Metabolism ; Proteins–Metabolism ; Thermodynamics–Metabolism ; Ligands ; Proteins ; Arginine ; Guanidine
languageeng
source
descriptionA database survey in this study revealed for the first time that there are 227 counterintuitive like-charge guanidinium pairings (Gdm super(+)-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 super(+)-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 super(+)-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 super(+)-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 super(+)-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.
version4
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1711537970/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Yang, Yang
1Xu, Zhijian
2Zhang, Zhengyan
3Yang, Zhuo
4Liu, Yingtao
5Wang, Jinan
6Cai, Tingting
7Li, Shujin
8Chen, Kaixian
9Shi, Jiye
10Zhu, Weiliang
titleLike-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?
subject
0Arginine–Metabolism
1Databases, Protein–Chemistry
2Drug Design–Metabolism
3Electrons–Pharmacology
4Guanidine–Chemistry
5Ligands–Metabolism
6Models, Molecular–Metabolism
7Protein Conformation–Metabolism
8Proteins–Metabolism
9Thermodynamics–Metabolism
10Ligands
11Proteins
12Arginine
13Guanidine
general
0English
110.1021/acs.jpcb.5b04130
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1711537970
issn
015205207
11520-5207
rsrctypearticle
creationdate2015
addtitleThe journal of physical chemistry. B
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributorYang, Yang
startdate20150910
enddate20150910
citationpf 11988 pt 11997 vol 119 issue 36
lsr30VSR-Enriched:[description, pqid, issn]
sort
titleLike-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?
authorYang, Yang ; Xu, Zhijian ; Zhang, Zhengyan ; Yang, Zhuo ; Liu, Yingtao ; Wang, Jinan ; Cai, Tingting ; Li, Shujin ; Chen, Kaixian ; Shi, Jiye ; Zhu, Weiliang
creationdate20150910
lso0120150910
facets
frbrgroupid8798839368119352266
frbrtype5
newrecords20181218
languageeng
creationdate2015
topic
0Arginine–Metabolism
1Databases, Protein–Chemistry
2Drug Design–Metabolism
3Electrons–Pharmacology
4Guanidine–Chemistry
5Ligands–Metabolism
6Models, Molecular–Metabolism
7Protein Conformation–Metabolism
8Proteins–Metabolism
9Thermodynamics–Metabolism
10Ligands
11Proteins
12Arginine
13Guanidine
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Yang, Yang
1Xu, Zhijian
2Zhang, Zhengyan
3Yang, Zhuo
4Liu, Yingtao
5Wang, Jinan
6Cai, Tingting
7Li, Shujin
8Chen, Kaixian
9Shi, Jiye
10Zhu, Weiliang
jtitlejournal of physical chemistry. B
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Yang
1Xu
2Zhang
3Liu
4Wang
5Cai
6Li
7Chen
8Shi
9Zhu
aufirst
0Yang
1Zhijian
2Zhengyan
3Zhuo
4Yingtao
5Jinan
6Tingting
7Shujin
8Kaixian
9Jiye
10Weiliang
au
0Yang, Yang
1Xu, Zhijian
2Zhang, Zhengyan
3Yang, Zhuo
4Liu, Yingtao
5Wang, Jinan
6Cai, Tingting
7Li, Shujin
8Chen, Kaixian
9Shi, Jiye
10Zhu, Weiliang
addauYang, Yang
atitleLike-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?
jtitleThe journal of physical chemistry. B
risdate20150910
volume119
issue36
spage11988
epage11997
pages11988-11997
eissn1520-5207
formatjournal
genrearticle
ristypeJOUR
doi10.1021/acs.jpcb.5b04130
urlhttp://search.proquest.com/docview/1711537970/
issn15206106
date2015-09-10