Reversible activation of a cell-penetrating peptide in a membrane environment

Journal of the American Chemical Society
Denise SchachTobias Weidner

Abstract

Cell-penetrating peptides (CPPs) are promising molecules as drug carriers. However, because their uptake mainly involves endocytic mechanisms, endosomal trapping of the carrier (and drug) remains a high barrier for biomedical applications. The viral fusion mimic GALA, a pH-triggered CPP, takes advantage of the decreasing pH during endosome maturation to selectively attack endosomal membranes. Below pH 6, the sequence folds into a helix and can disrupt membranes. In this study, we show that the lipid bilayer radius-of-curvature has a negligible effect on GALA-induced leakage kinetics and that GALA remains pH responsive after inserting into a lipid membrane. The peptide can be reversibly "switched" between its inactive and active states after incorporation into the hydrophobic environment of lipid membranes, even after substantially interacting with lipid chains. This ability makes GALA-based delivery a potentially safe and efficient strategy for endosomal escape.

References

Feb 28, 2001·Progress in Biophysics and Molecular Biology·A Barth
Sep 12, 2006·Trends in Cell Biology·P A Janmey, P K J Kinnunen
Mar 25, 2008·Biophysical Journal·Manuela ZoonensDonald M Engelman
Jun 24, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Eun Seong LeeYou Han Bae
Jun 23, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hiroto HatakeyamaHideyoshi Harashima
May 28, 2010·The Journal of Physical Chemistry. B·Khoi Tan NguyenZhan Chen
Jul 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tobias WeidnerDavid G Castner
Oct 14, 2010·Molecular Membrane Biology·Oleg A AndreevYana K Reshetnyak
May 4, 2011·Journal of the American Chemical Society·Li FuElsa C Y Yan
Aug 20, 2011·Biochimica Et Biophysica Acta·Eugene SerebryanyElsa C Y Yan
Feb 2, 2012·The Journal of Physical Chemistry. B·Bei Ding, Zhan Chen
May 9, 2012·Journal of the American Chemical Society·Tobias WeidnerDavid G Castner
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Lan YaoOleg A Andreev
Jun 4, 2013·Physical Chemistry Chemical Physics : PCCP·Tobias Weidner, David G Castner
Jan 1, 2012·Pharmaceuticals·Alfredo Erazo-OliverasJean-Philippe Pellois
Jun 19, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·I I RzeźnickaT Weidner
Nov 15, 2006·Surface Science Reports·Edward T Castellana, Paul S Cremer

❮ Previous
Next ❯

Citations

May 31, 2016·Biochimica Et Biophysica Acta·Johannes FranzTobias Weidner
Jun 9, 2016·Organic & Biomolecular Chemistry·A KashiwadaJ Hashimoto
Oct 19, 2017·Physical Chemistry Chemical Physics : PCCP·Michael A DonovanTobias Weidner
Jan 17, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Gyu Chan KimYan Lee
May 22, 2021·Advanced Drug Delivery Reviews·Zehua LiuHélder A Santos
Jul 23, 2021·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Yue ZhaoHarvey N Rutt
May 29, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Baixiong ZhangShuji Ye
Feb 19, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Thaddeus W GolbekTobias Weidner
Dec 24, 2020·The Journal of Physical Chemistry. B·Thaddeus W GolbekJoe E Baio

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.