Novel pH-Sensitive Cyclic Peptides

Authors

Dhammika Weerakkody, University of Rhode Island
Anna Moshnikova, University of Rhode IslandFollow
Naglaa Salem El-Sayed, University of Rhode Island
Ramona-Cosmina Adochite, University of Rhode Island
Gregory Slaybaugh, University of Rhode Island
Jovana Golijanin, University of Rhode Island
Rakesh K. Tiwari, University of Rhode Island
Oleg A. Andreev, University of Rhode IslandFollow
Keykavous Parang, University of Rhode IslandFollow
Yana Reshetnyak, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

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 pH-sensitive tool in investigation or targeting of acidic tissue.

Citation/Publisher Attribution

Weerakkody, D. et al. Novel pH-Sensitive Cyclic Peptides. Sci. Rep. 6, 31322; doi: 10.1038/srep31322 (2016).

Available at: https://doi.org/10.1038/srep31322

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Comment

Rakesh K. Tiwari and Naglaa Salem El-Sayed are affiliated with the Department of Biomedical and Pharmaceutical Sciences.

Dhammika Weerakkody, Anna Moshnikova, Ramona-Cosmina Adochite, Gregory Slaybaugh, Jovana Golijanin, Oleg A. Andreev, Keykavous Parang and Yana K. Reshetnyak are affiliated with the Department of Physics.