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.
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Myeong Seop
authors: MS
authors: Kim
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Yooran
authors: Y
authors: Ki
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Song Yeon
authors: SY
authors: Ahn
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Suyoung
authors: S
authors: Yoon
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sung-Eun
authors: SE
authors: Kim
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Hyeung-Geun
authors: HG
authors: Park
authors: Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
authors: Wei
authors: W
authors: Sun
authors: National Leading Research Lab of Molecular Modeling & Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Karam
authors: K
authors: Son
authors: National Leading Research Lab of Molecular Modeling & Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Minghua
authors: M
authors: Cui
authors: National Leading Research Lab of Molecular Modeling & Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Sun
authors: S
authors: Choi
authors: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Larry V
authors: LV
authors: Pearce
authors: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Timothy E
authors: TE
authors: Esch
authors: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Ian A
authors: IA
authors: Deandrea-Lazarus
authors: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Peter M
authors: PM
authors: Blumberg
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: jeewoo@snu.ac.kr.
authors: Jeewoo
authors: J
authors: Lee
mesh_terms: D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors*
chemical_list: D004224:Diterpenes; D008024:Ligands; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C024353:resiniferatoxin
keywords: Capsaicin; Molecular modeling; Resiniferatoxin; TRPV1 antagonist; Vanilloid receptor 1