77W. R. Kobertz ()
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical
School, 364 Plantation Street, 01605-2324 Worcester, MA, USA
e-mail: [email protected]
K. Mruk
Department of Chemical and Systems Biology, 269 Campus Drive, CCSR 3150,
Stanford, CA 94305, USA
e-mail: [email protected]
Bioreactive Tethers
Karen Mruk and William R. Kobertz
Abstract Ion channel complexes are challenging to study by traditional biochemi-
cal methods due to their membranous lipid environment and large size. Bioreactive
tethers are specialized chemical probes that have been used in electrophysiologi-
cal experiments to provide unique insight into ion channel structure and func-
tion. Because bioreactive tethers are small molecular probes, they can be used to
manipulate ion channel function in heterologous expression systems, native cells
and animal models. This chapter covers three classes of tethers: photoswitchable,
molecular rulers, and chemically reactive. The modular nature of bioreactive tethers
enables the facile synthesis of next generation reagents with enhanced functional-
ities to interrogate and control ion channels in novel and multifarious ways.
Keywords Azobenzene · Quaternary ammonium compounds · Ligands · Ion
channel blockers · Protein derivatization · Cysteine chemistry
1 Introduction
Ion channels are dynamic membrane-embedded protein complexes that produce
distinctive currents in response to changes in voltage, ligands, temperature, and
membrane deformation. These reliable and robust electrical signals have allowed
ion channel researchers to utilize chemical probes to exquisitely investigate the
structure, function, and modulation of ion channel complexes in living cells. One
class of chemical probes that have been particularly useful is the bioreactive tethers.
© Springer Science+Business Media New York 2015
C. Ahern, S. Pless (eds.), Novel Chemical Tools to Study Ion Channel Biology,
Advances in Experimental Medicine and Biology 869,
DOI 10.1007/978-1-4939-2845-3_5