Synthesis of nucleobase-functionalized -tripeptide scaffolds for higher ordered molecular architectures

Abstract

The stability of cyclic peptides and their self-assembling ability is an important aspect in the DNA recognition studies. Functionalization of cyclic peptides with nuclear bases may serve the purpose of mimicking and interacting with the DNA single strand. Stacking of the cyclic peptides after functionalzation may develop steric hinderance. L-Lysine, with side chain amino group, was selected to avoid these steric factors. Differently-protected L-lysine was transformed into its respective β-analogue using Arndt Eistert synthesis. These β-amino acids were utilized to synthesize cyclic β-tripeptide scaffolds through a multistep sequence. The scaffolds after deprotection were subjected to functionalization with the selected nuclear bases (adenine, thymine, cytosine and guanine) after conversion to their acetic acid derivatives. The nucleobase-functionalized cyclic β-tripeptide scaffolds were completely deprotected, purified by RP-HPLC and characterized by ESI and HRMS.