Understanding the Role of Polypeptide Backbone in Biological Systems

The polypeptide backbone plays a crucial role in determining the structure and function of biological molecules such as proteins and nucleic acids. One of the key mechanisms by which the backbone influences these properties is through hydrogen bonding (H-bonding) interactions. These interactions occur between the backbone carbonyls and N–H groups, where the H-bond donors and acceptors are paired with nearly straight geometry.

The unique properties of H-bonding interactions enable nature to construct precise three-dimensional structures of biological molecules. For instance, α-helices and β-sheets are formed through H-bonding between backbone carbonyls and N–H groups. The pattern of H-bond donors and acceptors within molecules capable of participating in multiple H-bonds provides specificity by ensuring H-bonding interactions between complementary molecules.

In contrast to other molecular forces such as hydrophobic and electrostatic interactions, the alignment of the donor-acceptor pair constituting a H-bond restricts the geometry of the interaction. Hydrogen bonding is one of the most important non-covalent molecular forces in biology, chemistry, and materials science.

Recent studies have demonstrated the utility of designing smart, cell-penetrating polymers that undergo acid-activated endosomal escape in living cells. The conformational change of triazole polypeptides in response to the donor-acceptor pattern was conclusively demonstrated using both experimental-based and simulation-based methods.

In this context, 1,2,3-triazole groups incorporated onto polypeptide side-chains serve as both H-bond donors and acceptors at neutral pH. This disrupts the α-helical conformation, enabling dynamic conformational changes. Synthetic polypeptides have received increasing attention due to their ability to form higher ordered structures similar to proteins.

Overall, the control over secondary structures of polypeptides is primarily accomplished by tuning side-chain hydrophobic or ionic interactions. This highlights the importance of understanding the role of polypeptide backbone in biological systems and its potential applications in designing new biomaterials with specific properties.

Polypeptide backbone