Chemical-Functional Diversity in Cell-Penetrating Peptides

Abstract

Cell-penetrating peptides (CPPs) are a promising tool to overcome cell membrane barriers. They have already been successfully applied as carriers for several problematic cargoes, like e.g. plasmid DNA and (si)RNA, opening doors for new therapeutics. Although several hundreds of CPPs are already described in the literature, only a few commercial applications of CPPs are currently available. Cellular uptake studies of these peptides suffer from inconsistencies in used techniques and other experimental conditions, leading to uncertainties about their uptake mechanisms and structural properties. To clarify the structural characteristics influencing the cell-penetrating properties of peptides, the chemical-functional space of peptides, already investigated for cellular uptake, was explored. For 186 peptides, a new cell-penetrating (CP)-response was proposed, based upon the scattered quantitative results for cellular influx available in the literature. Principal component analysis (PCA) and a quantitative structure-property relationship study (QSPR), using chemo-molecular descriptors and our newly defined CP-response, learned that besides typical well-known properties of CPPs, i.e. positive charge and amphipathicity, the shape, structure complexity and the 3D-pattern of constituting atoms influence the cellular uptake capacity of peptides.

Synthesis and Biological Properties of Fungal Glucosylceramide

“…These inverted micelles alter the characteristic bilayer structure and organization of plasma membranes, allowing a more flexible membrane and a massive influx or efflux of material [27] in and out of the cell during specific cellular insults. Interestingly, this phenomenon is linked to the geometrical and structural features of glycosphingolipids [28], [29] and plants have a variety of possibilities for the regulation of this phenomenon given their large number of GlcCer structures.…”

Exploring the chemical space of quorum sensing peptides

“…The chemical descriptors were calculated as previously described . Before calculating the different chemical properties of the Quorumpeps peptides ( n = 231, September 2014), the geometrical structure of these peptides was optimized using HyperChem 8.0 (Hypercube, Gainesville, FL, USA).…”

“…Multivariate data analyses were performed using principal component analysis (PCA) and hierarchical cluster analysis (HCA) with SIMCA‐P+ 12.0 (Umetrics AB, Umeå, Sweden) and SPSS 21.0 (IBM, IL, USA) software programs, respectively . To obtain a dendrogram of the chemical clustering (HCA), average‐linkage clustering was performed using the Euclidean distance as the dissimilarity criterion.…”

Modular sub-monomeric cell-penetrating guanidine-rich peptoids – synthesis, assembly and biological evaluation

“…From these pioneering works and based on the fundamentals of these observations, cell-penetrating peptides (CPPs) and CPPlike transporters have been further developed and diversied. 6 Promising proofs of concepts were made, demonstrating the feasibility to deliver otherwise impermeable cargoes to various cell types and tissues, including the brain, using such transporters. [7][8][9] CPPs were originally classied in three categories: cationic, amphipathic and lipophilic.…”