PMID- 24036313
OWN - NLM
STAT- MEDLINE
DCOM- 20141028
LR  - 20140825
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 144 Pt A
DP  - 2014 Oct
TI  - Design and synthesis of 2alpha-(tetrazolylethyl)-1alpha,25-dihydroxyvitamin D3 as a high 
      affinity ligand for vitamin D receptor.
PG  - 201-3
LID - S0960-0760(13)00161-1 [pii]
LID - 10.1016/j.jsbmb.2013.09.001 [doi]
AB  - X-ray cocrystallographic studies of the human vitamin D receptor 
      (hVDR)-[2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxyvitamin D3 (O1C3)] complex showed 
      that the terminal hydroxy group of the 2alpha-functional group of O1C3 formed a 
      hydrogen bond with Arg274 in the ligand binding domain (LBD) of hVDR to stabilize 
      the complex; therefore, O1C3 showed 3-times greater binding affinity for VDR than 
      the natural hormone. Here, the effects of a heteroaromatic ring on binding to 
      hVDR instead of the terminal OH group of O1C3 and also on preliminary biological 
      activities were studied. We synthesized 2alpha-[2-(tetrazol-2-yl)ethyl]-1alpha,25(OH)2D3 
      (1a) and its regioisomer 2alpha-[2-(tetrazol-1-yl)ethyl]-1alpha,25(OH)2D3 (1b), in which 
      1a showed much higher hVDR binding affinity and greater osteocalcin promoter 
      transactivation activity in human osteosarcoma (HOS) cells than those of 1b. 
      X-ray cocrystallographic analysis of the hVDR-1a complex showed new hydrogen bond 
      formation between one of the nitrogen atoms of the tetrazole ring and Arg274. 
      This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Matsuo, Miki
AU  - Matsuo M
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, 
      Tokyo 173-8605, Japan.
FAU - Hasegawa, Asami
AU  - Hasegawa A
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, 
      Tokyo 173-8605, Japan.
FAU - Takano, Masashi
AU  - Takano M
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, 
      Tokyo 173-8605, Japan.
FAU - Saito, Hiroshi
AU  - Saito H
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Kakuda, Shinji
AU  - Kakuda S
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Takagi, Kenichiro
AU  - Takagi K
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Ochiai, Eiji
AU  - Ochiai E
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Horie, Kyohei
AU  - Horie K
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Takimoto-Kamimura, Midori
AU  - Takimoto-Kamimura M
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Takenouchi, Kazuya
AU  - Takenouchi K
AD  - Teijin Institute for Bio-medical Research, Teijin Pharma Ltd., 4-3-2 Asahigaoka, 
      Hino, Tokyo 191-8512, Japan.
FAU - Sawada, Daisuke
AU  - Sawada D
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, 
      Tokyo 173-8605, Japan.
FAU - Kittaka, Atsushi
AU  - Kittaka A
AD  - Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, 
      Tokyo 173-8605, Japan. Electronic address: akittaka@pharm.teikyo-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130910
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (2-(2-(tetrazol-2-yl)ethyl)-1,25-dihydroxyvitamin D3)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Vitamins)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Antineoplastic Agents/*chemical synthesis/pharmacology
MH  - Bone Neoplasms/drug therapy/metabolism/pathology
MH  - Calcitriol/*analogs & derivatives/chemical synthesis/pharmacology
MH  - *Drug Design
MH  - Humans
MH  - Osteosarcoma/drug therapy/metabolism/pathology
MH  - Receptors, Calcitriol/*metabolism
MH  - Structure-Activity Relationship
MH  - Vitamins/*chemical synthesis/pharmacology
OTO - NOTNLM
OT  - 2alpha-Functionalized vitamin D
OT  - Binding affinity
OT  - Transactivation
OT  - Vitamin D receptor
OT  - Vitamin D(3)
OT  - X-ray cocrystallographic analysis
EDAT- 2013/09/17 06:00
MHDA- 2014/10/29 06:00
CRDT- 2013/09/17 06:00
PHST- 2013/07/23 00:00 [received]
PHST- 2013/08/28 00:00 [revised]
PHST- 2013/09/02 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/10/29 06:00 [medline]
AID - S0960-0760(13)00161-1 [pii]
AID - 10.1016/j.jsbmb.2013.09.001 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:201-3. doi: 
      10.1016/j.jsbmb.2013.09.001. Epub 2013 Sep 10.