Rapid translocation of amphipathic βhelical and β-sheet-forming peptides through plasma membranes of endothelial cells

Oehlke, J.; Scheller, Anne; Janek, Katharina; Wiesner, Burkhard; Krause, Eberhard; Beyermann, Michael; Bienert, Michael

doi:10.1007/0-306-46864-6_268

Cited by 3 publications

(2 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although most of the amphipathic CPPs possess a net positive charge, there is evidence that the actual uptake process is driven by the amphiphilicity per se and not just by electrostatic accumulation on the anionic cell surface. Studies with the “sweet arrow peptide” (SAP) and its all-Arg/all-Glu analogue SAP(E), a neutral and an anionic analogue of the model amphipathic peptide (MAP), had shown that as long as the amphipathic character of the peptide is maintained, its cell-penetrating capacity is also preserved. ,− Therefore, we incorporated a variant of MAP that had been rationally designed with a cationic secondary amphipathic character . We named this C-terminally amidated analogue 4 (MAP-1) (KLALKALKALKAALKLA-NH 2 ) .…”

Section: Resultsmentioning

confidence: 99%

Lactam-Stapled Cell-Penetrating Peptides: Cell Uptake and Membrane Binding Properties

et al. 2017

View full text Add to dashboard Cite

Stapling of side chains to stabilize an α-helical structure has been generally associated with an increased uptake of CPPs. Here, we compare four amphiphilic stapled peptides with their linear counterparts in terms of their membrane binding and conformational features in order to correlate these with uptake efficiency and toxicological effects. The impact of lactam stapling was found to vary strongly with regard to the different aspects of peptide-membrane interactions. Nearly all stapled peptides caused less membrane perturbation (vesicle leakage, hemolysis, bacterial lysis) than their linear counterparts. In one case (MAP-1) where stapling enhanced α-helicity in aqueous and lipid environments, leakage was eliminated while cell uptake in HEK293 and HeLa cells remained high, which improved the overall characteristics. The other systems (DRIM, WWSP, KFGF) did not improve, however. The data suggest that cell uptake of amphipathic CPPs correlates with their adopted α-helix content in membranes rather than their helicity in solution.

show abstract

Section: Resultsmentioning

confidence: 99%

Lactam-Stapled Cell-Penetrating Peptides: Cell Uptake and Membrane Binding Properties

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The structure of a MAP allows positioning of hydrophilic and hydrophobic residues on opposite sides, which, in the right conditions, can adopt a stable α-helix structure, getting close to lipidic membrane in temperatures between 25 and 55 °C [ 36 , 37 ], and even a β-structure with increased pressure and concentration [ 7 , 38 ]. In addition, MAPs are characterized by an overall positive net charge of five [ 39 ] and are very stable at physiological conditions associated with slow blood clearance (half-life above 72 h) in in vivo studies [ 40 ]. The authors demonstrated that arginine and arginine bonds (RR bonds) could lead to degradation susceptibility of peptides, thus showing that peptides not containing RR bonds demonstrated more stability that those with RR bonds in the sequence [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

A Second Life for MAP, a Model Amphipathic Peptide

Silva

Kurrikoff

Langel

et al. 2022

IJMS

View full text Add to dashboard Cite

Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future.

show abstract

Cell-Penetrating Peptides: a Useful Tool for the Delivery of Various Cargoes Into Cells

Böhmová

Machová²,

Pechar³

et al. 2018

Physiol Res

View full text Add to dashboard Cite

Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies.

show abstract

Rapid translocation of amphipathic βhelical and β-sheet-forming peptides through plasma membranes of endothelial cells

Cited by 3 publications

References 4 publications

Lactam-Stapled Cell-Penetrating Peptides: Cell Uptake and Membrane Binding Properties

Lactam-Stapled Cell-Penetrating Peptides: Cell Uptake and Membrane Binding Properties

A Second Life for MAP, a Model Amphipathic Peptide

Cell-Penetrating Peptides: a Useful Tool for the Delivery of Various Cargoes Into Cells

Contact Info

Product

Resources

About