Synthesis of dimeric analogs of adenophostin A that potently evoke Ca2+ release through IP3 receptors. Issue 89 (12th September 2016)

• Record Type: Journal Article
• Authors: Vibhute, Amol M.; Pushpanandan, Poornenth; Varghese, Maria; Koniecnzy, Vera; Taylor, Colin W.; Sureshan, Kana M.
• Is Part Of: RSC advances. Volume 6:Issue 89(2016)
• Page Start: 86346
• Page End: 86351
• Publication Date: 2016-09-12
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra19413c
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Syntheses and Ca 2+ release potentials of four dimeric analogs of adenophostin A (AdA) through activation of type 1 IP3 R are reported. These analogs are full agonists of IP3 R and are equipotent to AdA, the most potent agonist of IP3 R. Abstract : Inositol 1, 4, 5-trisphosphate receptors (IP3 Rs) are tetrameric intracellular channels through which many extracellular stimuli initiate the Ca 2+ signals that regulate diverse cellular responses. There is considerable interest in developing novel ligands of IP3 R. Adenophostin A (AdA) is a potent agonist of IP3 R and since some dimeric analogs of IP3 R 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 Ca 2+ through type 1 IP3 R and established that the newly synthesized dimers are equipotent to AdA and triazolophostin.