Replacement of Ala by Aib Improves Structuration and Biological Stability in Thymine-Based Nucleopeptides

摘要

Nucleopeptides containing alanyl-nucleoamino acids, carrying nucleobases at their side-chains, are a recently developed class of nucleic acid analogs displaying promising biological properties [1]. We have recently used a-aminoisobutyric acid (Aib, Figure 1), a sterically hindered C~αtetrasubstituted a-amino acid promoting the adoption of helical structures [2], to freeze the conformational freedom of nucleopeptides [3]. In this communication we report the effects of the presence of Aib residues on the conformation and the biological properties of thymine-based nucleopeptides. Three water-soluble nucleo-heptapeptides have been synthesized (Figure 1): T2A, carrying two AlaT, one Lys and four Ala residues; T2U, in which the central Ala residue is replaced by an Aib residue, and 6TTK, in which all Ala residues are replaced by Aib residues.