Many polycationic cell penetrating peptides (CPPs) have been effectively utilised as intracellular delivery vectors. Common CPP sequences such as Tat, Penetratin and Transportan-10 are highly efficient vectors that can access intracellular compartments with minimal cellular toxicity when employed at concentrations achievable in vivo. Thus, CPPs can be engineered to enhance the intracellular delivery of a range of bioactive cargoes which vary in size from small drugs to whole proteins.
It is likely that intrinsic cell penetrating sequences, alternatively described as transduction domains, could enable structurally diverse proteins to translocate biological membranes - a mechanistic process analogous to the intercellular shuttling of transcription factors. Furthermore, the sites of protein-protein interactions (PPIs), often containing polycationic micro-domains, represent a viable therapeutic modality. PPIs are considered intractable to small drugs but can be effectively targeted with more extended peptides including helical sequences. Thus, there is tremendous scope to develop bioactive CPPs or biportides that can selectively modulate the activities of intracellular proteins. One common approach is to utilise a sychnologically-organised chimeric peptide consisting of a distinct CPP vector extended with a known bioactive sequence. Other bioportides present multiple pharmacophores for cellular penetration and biological activities that are discontinuously organised within the primary structure. The term rhegnylogic is a useful descriptor to delineate this latter class of bioportide. Thus, recent years have witnessed a tremendous increase in the description of bioportides that can modulate cellular dynamics. Methodologies to target CPPs and bioportides to therapeutic sites include the application of receptor ligands and other homing sequences.
This presentation will provide a succinct overview of developments that support the contention that bioportides exhibit tremendous potential for the development of research tools and potential therapeutics.