Guanophostin A: Synthesis and evaluation of a high affinity agonist of the d-myo-inositol 1,4,5-trisphosphate receptor

Abstract

Guanophostin A, the guanosine counterpart of the inositol 1,4,5-trisphosphate receptor agonist adenophostin A, has been synthesized and is the first synthetic adenophostin A-like analogue to be equipotent to its parent in stimulating intracellular Ca²⁺ release; its nucleotide moiety is proposed to interact with the receptor binding core by guanine base cation-π stacking with Arg504 and hydrogen bonding with Glu505 and interaction of the ribosyl 2′-phosphate group with the helix-dipole of α₆.