Optical control of L-type Ca2+ channels using a diltiazem photoswitch

被引：44

作者：

Fehrentz, Timm ^{[1
]}

Huber, Florian M. E. ^{[2
,3
,15
]}

Hartrampf, Nina ^{[2
,3
]}

Bruegmann, Tobias ^{[4
,5
]}

Frank, James A. ^{[2
,3
,16
]}

Fine, Nicholas H. F. ^{[6
,7
,8
]}

Malan, Daniela ^{[4
]}

Danzl, Johann G. ^{[9
,17
]}

Tikhonov, Denis B. ^{[10
]}

Sumser, Martin ^{[2
,3
]}

Sasse, Philipp ^{[4
]}

Hodson, David J. ^{[6
,7
,8
]}

Zhorov, Boris S. ^{[10
,11
,12
]}

Klocker, Nikolaj ^{[1
]}

Trauner, Dirk ^{[2
,3
,13
,14
]}

机构：

[1] Univ Dusseldorf, Inst Neural & Sensory Physiol, Fac Med, Dusseldorf, Germany

[2] Univ Munich, Dept Chem, Munich, Germany

[3] Ctr Integrated Prot Sci CIPSM, Munich, Germany

[4] Univ Bonn, Fac Med, Inst Physiol 1, Bonn, Germany

[5] Univ Bonn, Res Training Grp 1873, Bonn, Germany

[6] Univ Birmingham, IMSR, Birmingham, W Midlands, England

[7] Univ Birmingham, Ctr Membrane Prot & Receptors COMPARE, Birmingham, W Midlands, England

[8] Birmingham Hlth Partners, Ctr Endocrinol Diabet & Metab, Birmingham, W Midlands, England

[9] Max Planck Inst Biophys Chem, Dept NanoBiophoton, Gottingen, Germany

[10] Russian Acad Sci, Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg, Russia

[11] Almazov Fed Heart Blood & Endocrinol Ctr, Inst Mol Biol & Genet, St Petersburg, Russia

[12] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON, Canada

[13] NYU, Dept Chem, New York, NY 10003 USA

[14] NYU, Inst Neurosci, New York, NY USA

[15] Roche Diagnost GmbH, DXRERA, Penzberg, Germany

[16] MIT, Elect Res Lab, Cambridge, MA 02139 USA

[17] IST Austria, Klosterneuburg, Austria

来源：

NATURE CHEMICAL BIOLOGY | 2018年 / 14卷 / 08期

基金：

英国惠康基金; 加拿大自然科学与工程研究理事会; 俄罗斯科学基金会;

关键词：

CELL ELECTRICAL-ACTIVITY; CALCIUM-CHANNELS; K+ CHANNELS; SODIUM; PHYSIOLOGY; MECHANISM; GLUCOSE; BINDING; BLOCK; SITE;

D O I：

10.1038/s41589-018-0090-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic beta-cell function and cardiac activity under optical control.

引用

页码：764 / +

页数：7

共 30 条

[1] TABLES OF BOND LENGTHS DETERMINED BY X-RAY AND NEUTRON-DIFFRACTION .1. BOND LENGTHS IN ORGANIC-COMPOUNDS [J].

ALLEN, FH ;

KENNARD, O ;

WATSON, DG ;

BRAMMER, L ;

ORPEN, AG ;

TAYLOR, R .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1987, (12) :S1-S19

[2] Retrograde heart perfusion: The Langendorff technique of isolated heart perfusion [J].

Bell, Robert M. ;

Mocanu, Mihaela M. ;

Yellon, Derek M. .

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2011, 50 (06) :940-950

[3] Optogenetic control of heart muscle in vitro and in vivo [J].

Bruegmann, Tobias ;

Malan, Daniela ;

Hesse, Michael ;

Beiert, Thomas ;

Fuegemann, Christopher J. ;

Fleischmann, Bernd K. ;

Sasse, Philipp .

NATURE METHODS, 2010, 7 (11) :897-U45

[4]

Catterall WA, 2017, NAT CHEM BIOL, V13, P455, DOI [10.1038/NCHEMBIO.2353, 10.1038/nchembio.2353]

[5] TOLBUTAMIDE AS MIMIC OF GLUCOSE ON BETA-CELL ELECTRICAL-ACTIVITY - ATP-SENSITIVE K+ CHANNELS AS COMMON PATHWAY FOR BOTH STIMULI [J].

COOK, DL ;

IKEUCHI, M .

DIABETES, 1989, 38 (04) :416-421

[6] THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].

DEWAR, MJS ;

ZOEBISCH, EG ;

HEALY, EF ;

STEWART, JJP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909

[7] Optical control of GPR40 signalling in pancreatic β-cells [J].

Frank, James Allen ;

Yushchenko, Dmytro A. ;

Fine, Nicholas H. F. ;

Duca, Margherita ;

Citir, Mevlut ;

Broichhagen, Johannes ;

Hodson, David J. ;

Schultz, Carsten ;

Trauner, Dirk .

CHEMICAL SCIENCE, 2017, 8 (11) :7604-7610

[8]

FREEDMAN SB, 1984, J NEUROSCI, V4, P1453

[9] Docking flexible ligands in proteins with a solvent exposure- and distance-dependent dielectric function [J].

Garden, Daniel P. ;

Zhorov, Boris S. .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2010, 24 (02) :91-105

[10]

GRISSMER S, 1994, MOL PHARMACOL, V45, P1227

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