A convenient method for synthesis of tetraoxazole peptide macrocycles

Abstract

G-quadruplex DNA plays important regulatory roles in the maintenance of telomere length and transcriptions inhibition of such oncogenes as c-myc, and thus has become an attractive target for the development of anti-cancer therapeutic agents. Poly-oxazole macrocycles are a promising new class of G-quadruplex binding ligands. Herein is described the synthesis of a tetraoxazole peptide macrocycle and an epimerization product. The synthetic unit was prepared by cyclization-oxidation of a diserine with one hydroxyl protected. Two-cycle coupling of the unit gave a linear tetraoxazole amide. The targeted molecule and the epimerization product were obtained after macrocyclization of the linear precursor and following removal of the protecting benzyl groups. With structural similarities to the most potent G-quadruplex stabilizer telomestatin, these two molecules might potentially be used to probe the biological significance of G-quadruplex' in vivo.