Conformational studies of β-amino acids, oligo- and polypeptides

Backbone modified β-amino acids are prime candidates to increase the half-life of peptides / drugs / hormones under physiological conditions. Their incorporation into polypeptides and proteins is possible without disrupting secondary structural element of proteins. These α/β-chimeras successfully resist against proteolysis quite effectively compared to the parent macromolecules. However, introducing additional main chain atom(s) clearly add to the complexity, conformational landscape and flexibility of these molecules. We have recently shown that replacing α-amino acids with conformationally constrained cyclic β-residues instead of their open-chain variants is, in some cases at least, preferred for sustaining the bioactive conformation and the in vivo activity of the parent compound. Systematic conformational search was therefore carried out for monomers and homohexamers of furanoid β-aminoacids. The hexamers of cis- and trans furanoid β-amino acids and β-sugar amino acids show great variability, though their secondary structure preference can often be foreseen form their building blocks.