Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands

Myeong Seop Kim; Yooran Ki; Song Yeon Ahn; Suyoung Yoon; Sung Eun Kim; Hyeung Geun Park; Wei Sun; Karam Son; Minghua Cui; Sun Choi; Larry V. Pearce; Timothy E. Esch; Ian A. Deandrea-Lazarus; Peter M. Blumberg; Jeewoo Lee

doi:10.1016/j.bmcl.2013.10.064

Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands

Myeong Seop Kim, Yooran Ki, Song Yeon Ahn, Suyoung Yoon, Sung Eun Kim, Hyeung Geun Park, Wei Sun, Karam Son, Minghua Cui, Sun Choi, Larry V. Pearce, Timothy E. Esch, Ian A. Deandrea-Lazarus, Peter M. Blumberg, Jeewoo Lee

Department of Pharmaceutical Sciences

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

10 Scopus citations

Abstract

The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.

Original language	English
Pages (from-to)	382-385
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2013.10.064
State	Published - 1 Jan 2014

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) Grant ( 2007-0056817 ) and NLRL program Grant ( 2011-0028885 ) funded by the Korea government MSIP, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270).

Keywords

Capsaicin
Molecular modeling
Resiniferatoxin
TRPV1 antagonist
Vanilloid receptor 1

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10.1016/j.bmcl.2013.10.064

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Kim, M. S., Ki, Y., Ahn, S. Y., Yoon, S., Kim, S. E., Park, H. G., Sun, W., Son, K., Cui, M., Choi, S., Pearce, L. V., Esch, T. E., Deandrea-Lazarus, I. A., Blumberg, P. M., & Lee, J. (2014). Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands. Bioorganic and Medicinal Chemistry Letters, 24(1), 382-385. https://doi.org/10.1016/j.bmcl.2013.10.064

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title = "Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands",

abstract = "The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.",

keywords = "Capsaicin, Molecular modeling, Resiniferatoxin, TRPV1 antagonist, Vanilloid receptor 1",

author = "Kim, {Myeong Seop} and Yooran Ki and Ahn, {Song Yeon} and Suyoung Yoon and Kim, {Sung Eun} and Park, {Hyeung Geun} and Wei Sun and Karam Son and Minghua Cui and Sun Choi and Pearce, {Larry V.} and Esch, {Timothy E.} and Deandrea-Lazarus, {Ian A.} and Blumberg, {Peter M.} and Jeewoo Lee",

note = "Funding Information: This research was supported by the National Research Foundation of Korea (NRF) Grant ( 2007-0056817 ) and NLRL program Grant ( 2011-0028885 ) funded by the Korea government MSIP, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270). ",

year = "2014",

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doi = "10.1016/j.bmcl.2013.10.064",

language = "English",

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pages = "382--385",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Kim, MS, Ki, Y, Ahn, SY, Yoon, S, Kim, SE, Park, HG, Sun, W, Son, K, Cui, M, Choi, S, Pearce, LV, Esch, TE, Deandrea-Lazarus, IA, Blumberg, PM & Lee, J 2014, 'Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands', Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 1, pp. 382-385. https://doi.org/10.1016/j.bmcl.2013.10.064

TY - JOUR

T1 - Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands

AU - Kim, Myeong Seop

AU - Ki, Yooran

AU - Ahn, Song Yeon

AU - Yoon, Suyoung

AU - Kim, Sung Eun

AU - Park, Hyeung Geun

AU - Sun, Wei

AU - Son, Karam

AU - Cui, Minghua

AU - Choi, Sun

AU - Pearce, Larry V.

AU - Esch, Timothy E.

AU - Deandrea-Lazarus, Ian A.

AU - Blumberg, Peter M.

AU - Lee, Jeewoo

N1 - Funding Information: This research was supported by the National Research Foundation of Korea (NRF) Grant ( 2007-0056817 ) and NLRL program Grant ( 2011-0028885 ) funded by the Korea government MSIP, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270).

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.

AB - The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.

KW - Capsaicin

KW - Molecular modeling

KW - Resiniferatoxin

KW - TRPV1 antagonist

KW - Vanilloid receptor 1

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AN - SCOPUS:84891496656

SN - 0960-894X

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EP - 385

JO - Bioorganic and Medicinal Chemistry Letters

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IS - 1

ER -

Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands

Abstract

Bibliographical note

Keywords

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