Novel pH-Sensitive Cyclic Peptides

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

Research output: Contribution to journalArticlepeer-review

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)4 WC], and asymmetric, c[E4 W5 C], 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[E4 W5 C], at 24 hours after intravenous administration. pH-insensitive cyclic peptide c[R4 W5 C], 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.

Original languageEnglish (US)
Article number31322
JournalScientific Reports
Volume6
DOIs
StatePublished - Aug 12 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Novel pH-Sensitive Cyclic Peptides'. Together they form a unique fingerprint.

Cite this