Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors

Standard

Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors : a case of free fatty acid receptor 1 agonists. / Lukin, Alexey; Bakholdina, Anna; Chudinov, Mikhail; Onopchenko, Oleksandra; Zhuravel, Elena; Zozulya, Sergey; Gureev, Maxim; Krasavin, Mikhail.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 36, No. 1, 2021, p. 1651-1658.

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

Author

Lukin, Alexey ; Bakholdina, Anna ; Chudinov, Mikhail ; Onopchenko, Oleksandra ; Zhuravel, Elena ; Zozulya, Sergey ; Gureev, Maxim ; Krasavin, Mikhail. / Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors : a case of free fatty acid receptor 1 agonists. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2021 ; Vol. 36, No. 1. pp. 1651-1658.

BibTeX

@article{f9e60312498145118f34b2de8e070a60,

title = "Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors: a case of free fatty acid receptor 1 agonists",

abstract = "A set of 1,3,4-thiadiazole-2-carboxamides bearing a substituted biphenyl in the amide portion was synthesised and tested for agonistic activity towards free fatty acid receptor 1 (FFA1). The observed activity trends were impossible to rationalised based solely on the docking energy scores of Glide SP. On the contrary, when the phospholipid cell membrane bilayer was reconstructed around FFA1, it became apparent that inactive compounds displayed significant strained contacts with the membrane while for active compounds the strain was noticeably lower. These findings justify using the improved docking protocol for modelling GPCR-ligand interactions which uses the crystal structure of the receptor and a reconstructed portion of a cell membrane.",

keywords = "docking score, free fatty acid receptor 1 agonist, G protein-coupled receptor, phospholipid cell membrane bilayer, strained ligand interactions with cell membrane, INSULIN-SECRETION, GPR40 AGONISTS",

author = "Alexey Lukin and Anna Bakholdina and Mikhail Chudinov and Oleksandra Onopchenko and Elena Zhuravel and Sergey Zozulya and Maxim Gureev and Mikhail Krasavin",

note = "Funding Information: This research was supported by the Russian Foundation for Basic Research [project grants 19?33-90169 to Alexei Lukin and 21?53-12001 to Mikhail Krasavin]. We are grateful to the Center for Chemical Analysis and Materials Research of Saint-Petersburg State University for providing high-resolution mass-spectrometry data. Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2021",

doi = "10.1080/14756366.2021.1955874",

language = "English",

volume = "36",

pages = "1651--1658",

journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",

issn = "1475-6366",

publisher = "Taylor & Francis",

number = "1",

}

RIS

TY - JOUR

T1 - Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors

T2 - a case of free fatty acid receptor 1 agonists

AU - Lukin, Alexey

AU - Bakholdina, Anna

AU - Chudinov, Mikhail

AU - Onopchenko, Oleksandra

AU - Zhuravel, Elena

AU - Zozulya, Sergey

AU - Gureev, Maxim

AU - Krasavin, Mikhail

N1 - Funding Information: This research was supported by the Russian Foundation for Basic Research [project grants 19?33-90169 to Alexei Lukin and 21?53-12001 to Mikhail Krasavin]. We are grateful to the Center for Chemical Analysis and Materials Research of Saint-Petersburg State University for providing high-resolution mass-spectrometry data. Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2021

Y1 - 2021

N2 - A set of 1,3,4-thiadiazole-2-carboxamides bearing a substituted biphenyl in the amide portion was synthesised and tested for agonistic activity towards free fatty acid receptor 1 (FFA1). The observed activity trends were impossible to rationalised based solely on the docking energy scores of Glide SP. On the contrary, when the phospholipid cell membrane bilayer was reconstructed around FFA1, it became apparent that inactive compounds displayed significant strained contacts with the membrane while for active compounds the strain was noticeably lower. These findings justify using the improved docking protocol for modelling GPCR-ligand interactions which uses the crystal structure of the receptor and a reconstructed portion of a cell membrane.

AB - A set of 1,3,4-thiadiazole-2-carboxamides bearing a substituted biphenyl in the amide portion was synthesised and tested for agonistic activity towards free fatty acid receptor 1 (FFA1). The observed activity trends were impossible to rationalised based solely on the docking energy scores of Glide SP. On the contrary, when the phospholipid cell membrane bilayer was reconstructed around FFA1, it became apparent that inactive compounds displayed significant strained contacts with the membrane while for active compounds the strain was noticeably lower. These findings justify using the improved docking protocol for modelling GPCR-ligand interactions which uses the crystal structure of the receptor and a reconstructed portion of a cell membrane.

KW - docking score

KW - free fatty acid receptor 1 agonist

KW - G protein-coupled receptor

KW - phospholipid cell membrane bilayer

KW - strained ligand interactions with cell membrane

KW - INSULIN-SECRETION

KW - GPR40 AGONISTS

UR - http://www.scopus.com/inward/record.url?scp=85111009255&partnerID=8YFLogxK

U2 - 10.1080/14756366.2021.1955874

DO - 10.1080/14756366.2021.1955874

M3 - Article

AN - SCOPUS:85111009255

VL - 36

SP - 1651

EP - 1658

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 1

ER -

ID: 84591925