Collect. Czech. Chem. Commun. 1989, 54, 760-771

Synthesis, conformational features and biological activity of [Pro3] antiarrhythmic peptide

Bijoy Kundu

Division of Biopolymers, Central Drug Research Institute, Lucknow 226 001, India


Synthesis of Gly-Pro-Pro-Gly-Ala-Gly([Pro3]AAP) in solution has been carried out. Solvent dependent conformational distribution of [Pro3]AAP has been studied using CD and NMR spectroscopy. The CD spectra in water, methanol and trifluoroethanol show predominance of the polyproline II-like structure. The CD curve of [Pro3]AAP in aqueous solution suggests an absence of any intramolecular H-bonded conformation whereas in polar organic solvents like methanol and trifluoroethanol, a possible contribution from an intramolecularly H-bonded γ-turn around the Pro3 residue has been proposed. Solvent titration experiments in methanol-water system using 13C NMR suggest that all the carbonyls are exposed and are not involved in any ordered structure. Further, the Δδβγ values for both the prolines corresponded to the dihedral angle of 150° for polyproline II-like structure, thereby suggesting that in solution [Pro3]AAP exists predominantly in polyproline II-like structure. Temperature coefficients of NH chemical shifts in (CD3)2SO also indicate that all the NH's are exposed and are not involved in any intramolecular H-bonded structure. The antiarrhythmic, as well as antithrombotic activity of [Pro3]AAP have also been discussed.