Functional Role of β-Turn in Polypeptide Structure and its use as Template to Design Therapeutic Agents
Boutaina El Abida,
Since proteins and peptides play critical roles in many biological phenomena, their use as drugs is of great interest. However, their development is limited due to their poor bioavailability, antigenicity and unfavorable pharmacokinetics. In the majority of cases, not all domains of proteins are essential protein-protein interactions necessary for biological activities but only small regions of their folded structure, perform the interactions. Usually, these particular secondary structures are β-turns, occurring on the exposed surface of proteins, constitute the functional elements involved in molecular recognition processes between proteins, and in interactions between ligands and receptors. Moreover, there are also several examples of the design of modified peptides as therapeutic agents by mimicking β-turn structures. In view of this, this review will be focused on the importance of β-turn in some biological phenomena, such as prohormone proteolytic processing. This report will also address the use of β-turn mimicking strategies and its application in the design of potent peptide analogues which play an equally important role. Due to the optimal surface conformation, β-turn mimetics lead to productive interaction with receptors and antibodies.
Keywords: β-Turn, secondary structure, receptor, analog, posttranslational modification, prohormone convertases, precursor, substrate dynamics
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