Document Type
Article
Publication Date
8-12-2016
Abstract
A series of cyclic peptides containing a number of tryptophan (W) and glutamic acid (E) residues were synthesized and evaluated as pH-sensitive agents for targeting of acidic tissue and pH-dependent cytoplasmic delivery of molecules. Biophysical studies revealed the molecular mechanism of peptides action and localization within the lipid bilayer of the membrane at high and low pHs. The symmetric, c[(WE)4WC], and asymmetric, c[E4W5C], cyclic peptides translocated amanitin, a polar cargo molecule of similar size, across the lipid bilayer and induced cell death in a pH- and concentration-dependent manner. Fluorescently-labelled peptides were evaluated for targeting of acidic 4T1 mammary tumors in mice. The highest tumor to muscle ratio (5.6) was established for asymmetric cyclic peptide, c[E4W5C], at 24 hours after intravenous administration. pH-insensitive cyclic peptide c[R4W5C], where glutamic acid residues (E) were replaced by positively charged arginine residues (R), did not exhibit tumor targeting. We have introduced a novel class of cyclic peptides, which can be utilized as a new pHsensitive tool in investigation or targeting of acidic tissue.
Recommended Citation
Weerakkody, D. et al. Novel pH-Sensitive Cyclic Peptides. Sci. Rep. 6, 31322; doi: 10.1038/srep31322 (2016).
Supplementary Information
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The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
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Amino Acids, Peptides, and Proteins Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutical Preparations Commons, Pharmaceutics and Drug Design Commons
Comments
This article was originally published in Scientific Reports, volume 6, in 2016. DOI: 10.1038/srep31322