A new biology of cell penetrating peptides

Abstract

As pharmacokinetic modifiers, cell penetrating peptides (CPPs) have proven utility for the delivery of otherwise impermeable cargoes into the discrete intracellular compartments of eukaryotic cells. Methods for the molecular optimisation of CPP sequences can significantly increase the performance of novel vectors matched to a specific delivery function. Moreover, the ‘information rich’ composition and inherent molecular flexibility of many CPPs can also facilitate their interaction with intracellular proteins and other cellular structures. This proteomimetic property of CPPs has been exploited in the design of bioportides, bioactive CPPs that regulate cellular functions often by binding relatively flat PPI interfaces to achieve a dominant negative action. This new biology of CPPs is rapidly gathering momentum through the design and synthesis of a bewildering variety of peptides that may be, in whole or part, linear, helical, cyclic and/or chimeric in nature. A particular emphasis of contemporary CPP‐centred drug discovery is the unmet medical need of cancer, though the biomedical scope of bioportide applications is impressively broad including cellular signalling and reprogramming. We are hopeful that one or more of the fascinating studies described herein will translate into the clinic to establish bioportide technologies as a viable option for drug discovery.

Protein and peptide drug delivery system: A brief review

“…A number of CPPs including pVEC (H-LLIILRRRIRKQAHAHSK-NH2) plus a juxtamembrane protein component, deposits 615 to 6 32 out-of murine vascular endothelial cadherin, can be understood to cross round the blood-mind deterrent to dependably enter the cerebrum parenchyma. Inside this manner bioportide programs are not restricted to cells and tissues (Howl and Jones, 2020).…”

Artificial intelligence and machine learning in Leishmania drug discovery

“…Of these, nine research articles, ten reviews, and one editorial from 18 sources, the journal Current Topics in Medicinal Chemistry was the only one that submitted more than one document (three documents). Finally, all the documents found, after excluding the repeated ones, were as follows: [4,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. After reading the abstracts, the articles presented in Table 1 were selected.…”

Protein Mimicry and the Design of Bioactive Cell-Penetrating Peptides: The Genesis of STOPSPERM Bioportides

“…As recently reviewed [15], a variety of different strategies can be adopted to support the identification and molecular optimisation of bioportides. Cationic helices are a proven source of protein-mimetic bioportide sequences, most likely because such domains are commonly involved in PPIs at which sites the relative abundance of arginine is enriched.…”

“…Since the mature human spermatozoon is virtually incapable of genetic expression, bioportide technologies could be utilised to interrogate additional intracellular signalling mechanism that regulate unique features of sperm cell physiology including capacitation and fertilisation. Located within the space of all possible CPPs, bioportide space is now rapidly expanding [10,[12][13][14][15] to include STOPSPERM examples as prototypical male contraceptives. Navigation of this embryonic sector is accompanied by an appropriate music of the spheres, a mellifluous and descriptive refrain:…”