title: [(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.
abstract: 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.
authors.affiliation: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu University, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hosoya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kihara
authors.forename: Makoto
authors.initials: M
authors.lastname: Endo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: 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*
chemical_list: 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