New Linear Precursors of cIDPR Derivatives as Stable Analogs of cADPR: A Potent Second Messenger with Ca2+-Modulating Activity Isolated from Sea Urchin Eggs

Mar Drugs. 2019 Aug 17;17(8):476. doi: 10.3390/md17080476.

Abstract

Herein, we report on the synthesis of a small set of linear precursors of an inosine analogue of cyclic ADP-ribose (cADPR), a second messenger involved in Ca2+ mobilization from ryanodine receptor stores firstly isolated from sea urchin eggs extracts. The synthesized compounds were obtained starting from inosine and are characterized by an N1-alkyl chain replacing the "northern" ribose and a phosphate group attached at the end of the N1-alkyl chain and/or 5'-sugar positions. Preliminary Ca2+ mobilization assays, performed on differentiated C2C12 cells, are reported as well.

Keywords: C2C12 cells; IP3; cADPR; caffeine; calcium mobilization; neuroblastoma; phosphorylation; ryanodine receptors.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / drug effects*
  • Cell Differentiation / drug effects
  • Cyclic ADP-Ribose / metabolism*
  • Eggs
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sea Urchins / chemistry*
  • Second Messenger Systems / drug effects*
  • Structure-Activity Relationship

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Cyclic ADP-Ribose
  • Calcium