Synthesis and biological activity of atriopeptin III and its small molecular analog.

Atriopeptin III (AP III) and its small molecular analog were synthesized manually by stepwise solid-phase method. The peptides were oxidized with iodine in 30% acetic acid at very high dilution to form intramolecular disulfide bridge and purified to homogeneity by conventional means, including Sephadex G15, dialysis and reversed-phase HPLC. Bioassay study demonstrated that the synthetic AP III possesses potent bioactivities identical to those of the same product of Peninsula Lab both in vitro and in vivo; whereas the linear peptide, having the same primary structure as AP III, showed very limited bioactivity. The small analog, with Ser-Ser-residue deleted from the N-terminal of AP III, was equipotent as AP III while exhibiting a longer half-life in vivo resulting from the peptide modification.