Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

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Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act? / Schwartz, Thue W; Holst, Birgitte.

In: TIPS - Trends in Pharmacological Sciences, Vol. 28, No. 8, 2007, p. 366-73.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schwartz, TW & Holst, B 2007, 'Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?', TIPS - Trends in Pharmacological Sciences, vol. 28, no. 8, pp. 366-73. https://doi.org/10.1016/j.tips.2007.06.008

APA

Schwartz, T. W., & Holst, B. (2007). Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act? TIPS - Trends in Pharmacological Sciences, 28(8), 366-73. https://doi.org/10.1016/j.tips.2007.06.008

Vancouver

Schwartz TW, Holst B. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act? TIPS - Trends in Pharmacological Sciences. 2007;28(8):366-73. https://doi.org/10.1016/j.tips.2007.06.008

Author

Schwartz, Thue W ; Holst, Birgitte. / Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?. In: TIPS - Trends in Pharmacological Sciences. 2007 ; Vol. 28, No. 8. pp. 366-73.

Bibtex

@article{7f781ea0f2f911ddbf70000ea68e967b,
title = "Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?",
abstract = "Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites of several ordinary allosteric enhancers and ago-allosteric modulators seem to overlap with those of the endogenous agonists. Different molecular scenarios are proposed to explain this discrepancy from classical allosteric models. In one scenario, the ago-allosteric modulator can interchange between different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug.",
author = "Schwartz, {Thue W} and Birgitte Holst",
note = "Keywords: Allosteric Regulation; Binding Sites; Humans; Ligands; Models, Biological; Pharmaceutical Preparations; Protein Binding; Receptors, GABA; gamma-Aminobutyric Acid",
year = "2007",
doi = "10.1016/j.tips.2007.06.008",
language = "English",
volume = "28",
pages = "366--73",
journal = "Trends in Pharmacological Sciences",
issn = "0165-6147",
publisher = "Elsevier Ltd. * Trends Journals",
number = "8",

}

RIS

TY - JOUR

T1 - Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

AU - Schwartz, Thue W

AU - Holst, Birgitte

N1 - Keywords: Allosteric Regulation; Binding Sites; Humans; Ligands; Models, Biological; Pharmaceutical Preparations; Protein Binding; Receptors, GABA; gamma-Aminobutyric Acid

PY - 2007

Y1 - 2007

N2 - Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites of several ordinary allosteric enhancers and ago-allosteric modulators seem to overlap with those of the endogenous agonists. Different molecular scenarios are proposed to explain this discrepancy from classical allosteric models. In one scenario, the ago-allosteric modulator can interchange between different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug.

AB - Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites of several ordinary allosteric enhancers and ago-allosteric modulators seem to overlap with those of the endogenous agonists. Different molecular scenarios are proposed to explain this discrepancy from classical allosteric models. In one scenario, the ago-allosteric modulator can interchange between different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug.

U2 - 10.1016/j.tips.2007.06.008

DO - 10.1016/j.tips.2007.06.008

M3 - Journal article

C2 - 17629958

VL - 28

SP - 366

EP - 373

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

SN - 0165-6147

IS - 8

ER -

ID: 10149982