Fully flexible docking models of the complex between α7 nicotinic receptor and a potent heptapeptide inhibitor of the β-amyloid peptide binding

L. Michel Espinoza-Fonseca; José G. Trujillo-Ferrara

doi:10.1016/j.bmcl.2006.03.093

Fully flexible docking models of the complex between α7 nicotinic receptor and a potent heptapeptide inhibitor of the β-amyloid peptide binding

L. Michel Espinoza-Fonseca, José G. Trujillo-Ferrara

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

The heptapeptide IQTTWSR (IQ), recently reported as inhibitor of the β-amyloid (Aβ) binding to nicotinic acetylcholine receptors (nAChrs), was docked to the homology model of the α7 nicotinic acetylcholine receptor. The most representative models were further subjected to molecular dynamics simulations. The data obtained here suggest that Aβ needs highly specific structural motifs to bind to the α7nAChR. These structural motifs are located principally in the upper and lower surroundings of loop C, including loop F and sheets β1, β2, β6, β9, and β10 of the receptor. Overall, these results suggest that IQ can be mimicked by more bioavailable, stable compounds that would be helpful for the understanding of the Aβ binding site and its dynamics, and for the design of novel agents to be used as an effective alternative against Alzheimer's disease.

Original language	English (US)
Pages (from-to)	3519-3523
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2006.03.093
State	Published - Jul 1 2006
Externally published	Yes

Bibliographical note

Funding Information:
L.M.E.F. thanks the anonymous reviewers for their insight comments, David D. Thomas for his support and encouragement, and Asya Varbanova for her continuous support in proofreading the manuscript drafts. This work was supported, in part, by grants from CONACYT and CGPI-IPN to J.G.T.F.

Keywords

Alzheimer's disease
Docking
Drug design
Molecular dynamics simulations
α7 Nicotinic acetylcholine receptor
β-Amyloid peptide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.bmcl.2006.03.093

OpenUrl availability

Full text

Cite this

@article{08abe5042c704edfb4c574ad8ecaa2fa,

title = "Fully flexible docking models of the complex between α7 nicotinic receptor and a potent heptapeptide inhibitor of the β-amyloid peptide binding",

abstract = "The heptapeptide IQTTWSR (IQ), recently reported as inhibitor of the β-amyloid (Aβ) binding to nicotinic acetylcholine receptors (nAChrs), was docked to the homology model of the α7 nicotinic acetylcholine receptor. The most representative models were further subjected to molecular dynamics simulations. The data obtained here suggest that Aβ needs highly specific structural motifs to bind to the α7nAChR. These structural motifs are located principally in the upper and lower surroundings of loop C, including loop F and sheets β1, β2, β6, β9, and β10 of the receptor. Overall, these results suggest that IQ can be mimicked by more bioavailable, stable compounds that would be helpful for the understanding of the Aβ binding site and its dynamics, and for the design of novel agents to be used as an effective alternative against Alzheimer's disease.",

keywords = "Alzheimer's disease, Docking, Drug design, Molecular dynamics simulations, α7 Nicotinic acetylcholine receptor, β-Amyloid peptide",

author = "Espinoza-Fonseca, {L. Michel} and Trujillo-Ferrara, {Jos{\'e} G.}",

note = "Funding Information: L.M.E.F. thanks the anonymous reviewers for their insight comments, David D. Thomas for his support and encouragement, and Asya Varbanova for her continuous support in proofreading the manuscript drafts. This work was supported, in part, by grants from CONACYT and CGPI-IPN to J.G.T.F. ",

year = "2006",

month = jul,

day = "1",

doi = "10.1016/j.bmcl.2006.03.093",

language = "English (US)",

volume = "16",

pages = "3519--3523",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "13",

}

TY - JOUR

T1 - Fully flexible docking models of the complex between α7 nicotinic receptor and a potent heptapeptide inhibitor of the β-amyloid peptide binding

AU - Espinoza-Fonseca, L. Michel

AU - Trujillo-Ferrara, José G.

N1 - Funding Information: L.M.E.F. thanks the anonymous reviewers for their insight comments, David D. Thomas for his support and encouragement, and Asya Varbanova for her continuous support in proofreading the manuscript drafts. This work was supported, in part, by grants from CONACYT and CGPI-IPN to J.G.T.F.

PY - 2006/7/1

Y1 - 2006/7/1

N2 - The heptapeptide IQTTWSR (IQ), recently reported as inhibitor of the β-amyloid (Aβ) binding to nicotinic acetylcholine receptors (nAChrs), was docked to the homology model of the α7 nicotinic acetylcholine receptor. The most representative models were further subjected to molecular dynamics simulations. The data obtained here suggest that Aβ needs highly specific structural motifs to bind to the α7nAChR. These structural motifs are located principally in the upper and lower surroundings of loop C, including loop F and sheets β1, β2, β6, β9, and β10 of the receptor. Overall, these results suggest that IQ can be mimicked by more bioavailable, stable compounds that would be helpful for the understanding of the Aβ binding site and its dynamics, and for the design of novel agents to be used as an effective alternative against Alzheimer's disease.

AB - The heptapeptide IQTTWSR (IQ), recently reported as inhibitor of the β-amyloid (Aβ) binding to nicotinic acetylcholine receptors (nAChrs), was docked to the homology model of the α7 nicotinic acetylcholine receptor. The most representative models were further subjected to molecular dynamics simulations. The data obtained here suggest that Aβ needs highly specific structural motifs to bind to the α7nAChR. These structural motifs are located principally in the upper and lower surroundings of loop C, including loop F and sheets β1, β2, β6, β9, and β10 of the receptor. Overall, these results suggest that IQ can be mimicked by more bioavailable, stable compounds that would be helpful for the understanding of the Aβ binding site and its dynamics, and for the design of novel agents to be used as an effective alternative against Alzheimer's disease.

KW - Alzheimer's disease

KW - Docking

KW - Drug design

KW - Molecular dynamics simulations

KW - α7 Nicotinic acetylcholine receptor

KW - β-Amyloid peptide

UR - http://www.scopus.com/inward/record.url?scp=33646842340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646842340&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2006.03.093

DO - 10.1016/j.bmcl.2006.03.093

M3 - Article

C2 - 16621535

AN - SCOPUS:33646842340

SN - 0960-894X

VL - 16

SP - 3519

EP - 3523

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

Fully flexible docking models of the complex between α7 nicotinic receptor and a potent heptapeptide inhibitor of the β-amyloid peptide binding

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this