Issue 30, 2016

Structure–property relationships of photoresponsive inhibitors of the kinesin motor

Abstract

Recently we demonstrated the photoregulation of the activity of kinesin-1 using an azobenzene-tethered peptide (azo-peptide: Azo-Ile-Pro-Lys-Ala-Ile-Gln-Ala-Ser-His-Gly-Arg-OH). To understand the mechanism behind this photoswitchable inhibition, here we studied the structure–property relationships of a range of azo-peptides through systematic variations in the structures of the peptide and azobenzene units. The vital peptide sequence for kinesin inhibition—mediated through electrostatic, hydrophobic and C–Hπ interactions—was the same as that for the self-inhibition of kinesin. We also identified substituents on the azobenzene capable of enhancing the photoswitchability of inhibition. As a result, we developed a new inhibitor featuring a relatively short peptide unit (-Arg-Ile-Pro-Lys-Ala-Ile-Arg-OH) and an azobenzene unit bearing a para-OMe group. In the trans form of its azobenzene unit, this finely tuned inhibitor stopped the kinesin-driven gliding motility of microtubules completely at a relatively low concentration, yet allowed gliding motility with a relatively high velocity in the cis form obtained after UV irradiation.

Graphical abstract: Structure–property relationships of photoresponsive inhibitors of the kinesin motor

Supplementary files

Article information

Article type
Paper
Submitted
02 May 2016
Accepted
27 May 2016
First published
31 May 2016
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2016,14, 7202-7210

Structure–property relationships of photoresponsive inhibitors of the kinesin motor

A. S. Amrutha, K. R. S. Kumar, K. Matsuo and N. Tamaoki, Org. Biomol. Chem., 2016, 14, 7202 DOI: 10.1039/C6OB00951D

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