Design of dantrolene-derived probes for radioisotope-free photoaffinity labeling of proteins involved in the physiological Ca2+ release from sarcoplasmic reticulum of skeletal muscle.
Bifunctional dantrolene derivatives have been synthesized as probes for radioisotope-free photoaffinity labeling with the aim of elucidating the molecular mechanism of skeletal muscle contraction. GIF-0430 and GIF-0665 are aromatic azido-functionalized derivatives that were designed to selectively inhibit physiological Ca2+ release (PCR) from sarcoplasmic reticulum (SR) in mouse skeletal muscle without a strong effect on Ca2+-induced Ca2+ release (CICR). These photoaffinity probes consist of either an azidomethyl or an ethynyl group, respectively, which could function as a tag for introduction of an optional detectable marker unit by an appropriate chemoselective ligation method after the photo-cross-linking operation. Actually, the former probe worked to photolabel its target proteins specifically as confirmed by subsequent fluorescent visualization.
Hosoya
Takamitsu
T
Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan.
Hiramatsu
Toshiyuki
T
Ikemoto
Takaaki
T
Aoyama
Hiroshi
H
Ohmae
Tatsuro
T
Endo
Makoto
M
Suzuki
Masaaki
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D066298:In Vitro Techniques; D051379:Mice; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000494:pharmacology; D010777:Photochemistry; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012680:Sensitivity and Specificity
C501614:GIF-0162; C501613:GIF-0373; C501616:GIF-0430; C501615:GIF-0667; D019920:Photoaffinity Labels; D011506:Proteins; D003620:Dantrolene; D002118:Calcium