Journal
BIOCONJUGATE CHEMISTRY
Volume 32, Issue 5, Pages 950-957Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.1c00101
Keywords
-
Categories
Funding
- JSPS KAKENHI [JP18H04017, JP20H04707]
- JST CREST [JPMJCR18H5]
- JSPS Research Fellowship for Young Scientists
Ask authors/readers for more resources
Conjugating HAad with pyrenebutyric acid to form pBu-HAad can enhance intracellular protein delivery efficiency. Time-course and inhibitor studies suggest that anchoring HAad to the membrane with a pyrene moiety enhances peptide-membrane interaction, facilitating cytosolic translocation through membranes.
We previously reported an approach for intracellular protein delivery by attenuating membrane-lytic activity of cationic amphiphilic peptides on cell surfaces. HAad is one such peptides that cytosolically delivers proteins of interest, including antibodies, by stimulating their endosomal escape. Additionally, HAad elicits ruffling of cell membrane, accompanied by transient membrane permeabilization, allowing for the efficient cytosolic translocation of proteins. In this study, we prepared a conjugate of HAad with pyrenebutyric acid as a membrane-anchoring unit (pBu-HAad). pBu-HAad demonstrated protein delivery into cells with only 1/20 concentration of HAad. However, the conjugates with cholesteryl hemisuccinate and aliphatic fatty acids (C = 3, 6, and 10) did not yield such marked effects. The results of time-course and inhibitor studies suggest that the membrane anchoring of HAad by a pyrene moiety leads to enhanced peptide-membrane interaction and to loosen lipid packing, thus facilitating cytosolic translocation through membranes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available