Bioportides: Bioactive cell‐penetrating peptides that modulate cellular dynamics

Abstract

The study and exploitation of cell-penetrating peptides (CPPs) now extends into a third exciting decade. Pharmacokinetic modulators, including the more common sequences Tat, penetratin and transportan-10, markedly enhance the intracellular delivery of small drugs, peptides, oligonucleotides and proteins. We introduced the term bioportide to distinguish cell penetrant peptides with intrinsic bioactivities from more typically inert CPP vectors. Our first examples included rhegnylogically organised bioportides, monomeric peptides presenting pharmacophores for both cellular internalization and bioactivity discontinuously distributed within the primary sequence. However, it is conceptually expedient to employ the same terminology to encompass sychnologic bioportides that comprise an inert CPP vector conjugated to an otherwise impermeable bioactive peptide. In such cases the CPP provides an obvious address function whilst the bioactive cargo, often a protein mimetic sequence, is the message. Additional targeting sequences, usually added as chimeric extensions, can also be accommodated within the design of CPPs and bioportides to enable cell- and tissue-selective targeting. Thus, the identification and exploitation of bioportides provides further scope to employ CPPs as research tools, diagnostics and therapeutics spanning a range of pathologies.

Insights into the molecular mechanisms of action of bioportides: a strategy to target protein-protein interactions

“…However, there are now many examples of bioportides that display desirable biological activities and these are predominantly constructed from natural L amino acids (reviewed in Ref. 17). Thus, the term bioportide is a useful descriptor of many important research tools and a subset of those CPP-based peptides technologies, including Amgen's protein kinase C inhibitors, subject to clinical evaluation and intended for immune disorder therapy (Ref.…”

Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells

“…As indicated in Table 1, we compared common CPP vectors (Tat [5], penetratin [4], C105Y [19] and transportan 10 (TP10; [20])); mast cell secretagogues mastoparan (MP; [21]) and mitoparan (MitP; [22]); human cytochrome c-derived sequences (Cyt c [5][6][7][8][9][10][11][12][13] and Cyt c 77-101 [23]); the anti-angiogenic bioportide nosangiotide [6]; camptide [6], a known activator of G-proteins; and polycationic sequences within the primary structure of leucine rich repeat kinase 2 (LRRK2 1322-1340 and LRRK2 2413-2427 ). The sequences and sources of these peptides are provided in Table 1 and the references therein.…”

“…Some of the first examples of CPPs that were clearly effective pharmacokinetic modifiers included sequences related to penetratin (RQIKIWFQNRRMKWKK [4]) and Tat (GRKKRRQRRRPPQ [5]), polycationic peptides identified within helical domains of insect-and virally-encoded transcription factors respectively. More recently, CPPs with intrinsic bioactivities, now designated as bioportides [6], have also attracted significant attention as biomedical research tools and putative diagnostics and/or therapeutics (reviewed in [7]). …”

Microwave Assisted Peptide Synthesis of Some Rationally Designed Cell Penetrating Peptides from C-Kit Receptor

“…A recent genre of CPP, designated as bioportides, distinct from conventionally inert vectors, has been described. 8,9 these proteomimetic CPPs combine the dual properties of cellular penetration and biological activity and often derive from cationic helical domains of key signaling proteins and commonly act as biological modulators of protein-protein interactions (PPIs) [8][9][10][11].…”