[(125)I]-N-[(3-azido-5-iodo)benzyl]dantrolene and [(125)I]-N-[[3-iodo-5-(3-trifluoromethyl-3H-diazirin-3-yl)]benzyl]dantrolene: photoaffinity probes specific for the physiological Ca(2+) release from sarcoplasmic reticulum of skeletal muscle.
In order to capture and identify key molecules that regulate the release of Ca(2+) from the sarcoplasmic reticulum (SR) of skeletal muscle, we designed specific photoaffinity probes based on the structural modification of dantrolene. Thus, GIF-0082 and GIF-0276 possessing azido- and trifluoromethyldiazirinyl-benzyl groups, respectively, at the hydantoin moiety were found to have a highly selective inhibitory effect on physiological Ca(2+) release (PCR) without affecting Ca(2+)-induced Ca(2+) release (CICR). Successful realization of the sharp discrimination between PCR and CICR has led to the creation of [(125)I]GIF-0082 and [(125)I]GIF-0276, which were synthesized by substituting a stannyl group with (125)I in the corresponding phenylstannane precursors.
Hosoya
Takamitsu
T
Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu University, Japan.
Aoyama
Hiroshi
H
Ikemoto
Takaaki
T
Hiramatsu
Toshiyuki
T
Kihara
Yasutaka
Y
Endo
Makoto
M
Suzuki
Masaaki
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007457:Iodine Radioisotopes; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000502:physiology / Q000648:ultrastructure; D019920:Photoaffinity Labels / Q000138:chemical synthesis / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
C441780:GIF 0082; D007457:Iodine Radioisotopes; D009125:Muscle Relaxants, Central; C475583:N-((3-iodo-5-(3-trifluoromethyl-3H-diazirin-3-yl))benzyl)dantrolene; D019920:Photoaffinity Labels; D003620:Dantrolene; D002118:Calcium