Molecular peptide grafting as a tool for creating new generation of biopeptides: A mini-review

Molecular peptide grafting (MPG) is the isolation/synthesis of a bioactive fragment of a peptide/protein and its subsequent transfer to a target protein/peptide to create a new protein product with specified unique biological properties. This is one of the methods together with molecular stapling and peptide backbone circularization to strengthen the structural organization of short peptides. Nowadays research on MPT is mainly focused on demonstrating its usefulness and applicability, rather than on the development of next-generation biopeptides. The purpose of the mini-review is to demonstrate the applicability of MPT to create stable and bioavailable peptides of a new generation with enhanced biological properties. Choosing the right scaffold for subsequent inoculation of a biologically active peptide sequence into it is the most important task in creating targeted biopeptides. Peptides with the necessary framework, such as cyclotides, can be obtained by three-phase synthesis. Cyclotides have a common mechanism of action. Their biological activity is determined both by the ability to bind proteins with the formation of pores and destruction of biological target-membranes, and by the properties necessary to create new peptides in the scaffold. Various peptide inserts can be used to ensure the functionality of new biopeptides obtained by the MPT method. Different peptide drugs are an example of the effective practical use of MTP. Consequently, MPT makes it possible to effectively design a new generation of biopeptides characterized by high epitope thermodynamic and metabolic stability with new or enhanced biological functions. However, the effectiveness of the peptides obtained by the MPT must be proved in vitro and in vivo.