The Biological Implications of Threaded Protein Topologies - Abstract
Protein drugs are used to treat various diseases including cancer, autoimmune disorders, infectious diseases, and genetic disorders. They have an advantage to small molecules as they directly target specific proteins and receptors with great precision, minimizing off-target effects. This specificity can reduce the risk of side effects compared to small molecules, which often have broader interactions. One of the major challenges in protein- based therapeutics is the cost of production, administration, and storage limiting their accessibility. However, proteins can be engineered and
modified to enhance their properties, such as increasing their stability, altering their pharmacokinetics, or adding specific functionalities. Cyclic peptides have gained significant attention in drug design and development due to their unique properties and potential therapeutic benefits. Cyclic peptides are small proteins where the backbone forms a macrocycle. The novel class of proteins called pierced lasso topology (PLTs), may have an untapped potential in drug design as the biological activity is linked to conformational dynamics controlled by the threaded topology. Interestingly, the threaded topology is controlled by the redox potential fine-tuning biological activity on and off. In this review, we will discuss the role of PLTs in human health and their possible pharmaceutical applications.