title: Synthesis of dimeric analogs of adenophostin A that potently evoke Ca2+release through IP3receptors.
abstract: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are tetrameric intracellular channels through which many extracellular stimuli initiate the Ca2+signals that regulate diverse cellular responses. There is considerable interest in developing novel ligands of IP3R. Adenophostin A (AdA) is a potent agonist of IP3R and since some dimeric analogs of IP3R ligands are more potent than the corresponding monomer; we considered whether dimeric AdA analogs might provide agonists with increased potency. We previously synthesized traizolophostin, in which a simple triazole replaced the adenine of AdA, and showed it to be equipotent to AdA. Here, we used click chemistry to synthesize four homodimeric analogs of triazolophostin, connected by oligoethylene glycol chains of different lengths. We evaluated the potency of these analogs to release Ca2+through type 1 IP3R and established that the newly synthesized dimers are equipotent to AdA and triazolophostin.
authors.affiliation: School of Chemistry , Indian Institute of Science Education and Research Thiruvananthapuram , Kerala 695016 , India . Email: kms@iisertvm.ac.in ; http://kms514.wix.com/kmsgroup.
authors.forename: Amol M
authors.initials: AM
authors.lastname: Vibhute
authors.affiliation: School of Chemistry , Indian Institute of Science Education and Research Thiruvananthapuram , Kerala 695016 , India . Email: kms@iisertvm.ac.in ; http://kms514.wix.com/kmsgroup.
authors.forename: Poornenth
authors.initials: P
authors.lastname: Pushpanandan
authors.affiliation: School of Chemistry , Indian Institute of Science Education and Research Thiruvananthapuram , Kerala 695016 , India . Email: kms@iisertvm.ac.in ; http://kms514.wix.com/kmsgroup.
authors.forename: Maria
authors.initials: M
authors.lastname: Varghese
authors.affiliation: Department of Pharmacology , University of Cambridge , Tennis Court Road , Cambridge , CB2 1PD , UK.
authors.forename: Vera
authors.initials: V
authors.lastname: Koniecnzy
authors.affiliation: Department of Pharmacology , University of Cambridge , Tennis Court Road , Cambridge , CB2 1PD , UK.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Taylor
authors.affiliation: School of Chemistry , Indian Institute of Science Education and Research Thiruvananthapuram , Kerala 695016 , India . Email: kms@iisertvm.ac.in ; http://kms514.wix.com/kmsgroup.
authors.forename: Kana M
authors.initials: KM
authors.lastname: Sureshan