X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

X-ray structure based evaluation of analogs of citalopram : Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. / Topiol, Sid; Bang-Andersen, Benny; Sanchez, Connie; Plenge, Per; Loland, Claus J.; Juhl, Karsten; Larsen, Krestian; Bregnedal, Peter; Bogeso, Klaus P.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 27, No. 3, 01.02.2017, p. 470-478.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Topiol, S, Bang-Andersen, B, Sanchez, C, Plenge, P, Loland, CJ, Juhl, K, Larsen, K, Bregnedal, P & Bogeso, KP 2017, 'X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT', Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 3, pp. 470-478. https://doi.org/10.1016/j.bmcl.2016.12.037

APA

Topiol, S., Bang-Andersen, B., Sanchez, C., Plenge, P., Loland, C. J., Juhl, K., Larsen, K., Bregnedal, P., & Bogeso, K. P. (2017). X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. Bioorganic & Medicinal Chemistry Letters, 27(3), 470-478. https://doi.org/10.1016/j.bmcl.2016.12.037

CBE

Topiol S, Bang-Andersen B, Sanchez C, Plenge P, Loland CJ, Juhl K, Larsen K, Bregnedal P, Bogeso KP. 2017. X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. Bioorganic & Medicinal Chemistry Letters. 27(3):470-478. https://doi.org/10.1016/j.bmcl.2016.12.037

MLA

Vancouver

Author

Topiol, Sid ; Bang-Andersen, Benny ; Sanchez, Connie ; Plenge, Per ; Loland, Claus J. ; Juhl, Karsten ; Larsen, Krestian ; Bregnedal, Peter ; Bogeso, Klaus P. / X-ray structure based evaluation of analogs of citalopram : Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. In: Bioorganic & Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 3. pp. 470-478.

Bibtex

@article{872ed19cc2e9483e9a0eb81955022525,
title = "X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT",
abstract = "The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design. (C) 2016 Elsevier Ltd. All rights reserved.",
keywords = "Structure-based drug design, Computer-aided drug discovery, Docking, X-ray structure, SERT, DAT, LeuT, HUMAN SEROTONIN TRANSPORTER, BINDING-SITE, DOPAMINE TRANSPORTER, NEUROTRANSMITTER TRANSPORTERS, BACTERIAL HOMOLOG, UPTAKE INHIBITORS, 5-HT TRANSPORTER, IN-VIVO, ESCITALOPRAM, ANTIDEPRESSANTS",
author = "Sid Topiol and Benny Bang-Andersen and Connie Sanchez and Per Plenge and Loland, {Claus J.} and Karsten Juhl and Krestian Larsen and Peter Bregnedal and Bogeso, {Klaus P.}",
year = "2017",
month = feb,
day = "1",
doi = "10.1016/j.bmcl.2016.12.037",
language = "English",
volume = "27",
pages = "470--478",
journal = "Bioorganic & Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Pergamon Press",
number = "3",

}

RIS

TY - JOUR

T1 - X-ray structure based evaluation of analogs of citalopram

T2 - Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT

AU - Topiol, Sid

AU - Bang-Andersen, Benny

AU - Sanchez, Connie

AU - Plenge, Per

AU - Loland, Claus J.

AU - Juhl, Karsten

AU - Larsen, Krestian

AU - Bregnedal, Peter

AU - Bogeso, Klaus P.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design. (C) 2016 Elsevier Ltd. All rights reserved.

AB - The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design. (C) 2016 Elsevier Ltd. All rights reserved.

KW - Structure-based drug design

KW - Computer-aided drug discovery

KW - Docking

KW - X-ray structure

KW - SERT

KW - DAT

KW - LeuT

KW - HUMAN SEROTONIN TRANSPORTER

KW - BINDING-SITE

KW - DOPAMINE TRANSPORTER

KW - NEUROTRANSMITTER TRANSPORTERS

KW - BACTERIAL HOMOLOG

KW - UPTAKE INHIBITORS

KW - 5-HT TRANSPORTER

KW - IN-VIVO

KW - ESCITALOPRAM

KW - ANTIDEPRESSANTS

U2 - 10.1016/j.bmcl.2016.12.037

DO - 10.1016/j.bmcl.2016.12.037

M3 - Journal article

C2 - 28041833

VL - 27

SP - 470

EP - 478

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 3

ER -