Structure-property relationships of photoresponsive inhibitors of the kinesin motor.
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.
Research Institute for Electronic Science, Hokkaido University, N20, W10, Kita-Ku, Sapporo, Hokkaido, 001-0020, Japan. tamaoki@es.hokudai.ac.jp.
Ammathnadu S
AS
Amrutha
Research Institute for Electronic Science, Hokkaido University, N20, W10, Kita-Ku, Sapporo, Hokkaido, 001-0020, Japan. tamaoki@es.hokudai.ac.jp.
K R Sunil
KR
Kumar
Research Institute for Electronic Science, Hokkaido University, N20, W10, Kita-Ku, Sapporo, Hokkaido, 001-0020, Japan. tamaoki@es.hokudai.ac.jp.
Kazuya
K
Matsuo
Research Institute for Electronic Science, Hokkaido University, N20, W10, Kita-Ku, Sapporo, Hokkaido, 001-0020, Japan. tamaoki@es.hokudai.ac.jp.
Nobuyuki
N
Tamaoki
D000595:Amino Acid Sequence; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007536:Isomerism; D016547:Kinesins / Q000037:antagonists & inhibitors*; D008027:Light; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D061848:Optical Imaging / Q000379:methods; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D017319:Photosensitizing Agents / Q000037:antagonists & inhibitors*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D010455:Peptides; D017319:Photosensitizing Agents; D016547:Kinesins; C009850:azobenzene