A reagent-free, sequence-dependent in situ peptide self-cyclization strategy under physiological condition
Year: 2024
Type: article
Abstract: Cyclic peptides are an important class of bioactive molecules used as drugs as well as biomolecular probes . Peptide cyclization under the physiological environment, without added chemicals or reagents, would be a highly useful technique for in situ applications. A simple, highly efficient, and green procedure for side-chain to side-chain in situ peptide cyclization is established here at the physiological condition. The methodology further allows the release of small biologically active molecules through peptide self-cyclization. Bioactive molecules, as well as other organic leaving groups (having primary or secondary alcohol as a functional group), were conjugated to a short peptide RXE sequence (X = Pro/Ala/Gly). The peptides were designed to undergo cyclization under physiological conditions and release the covalently attached chemotherapeutic drug and nucleobases , in a controlled manner. In vitro studies were performed in detail, with optimized physiological parameters, to understand the kinetics as well as the mechanism of self-cyclization. The mechanism of action was investigated by HPLC and ESI-Mass spectrometry. The conformational change, due to cyclization of the peptides, was monitored by CD spectroscopy . The present concept of peptide self-cyclization leading to a bond cleavage could be a potential method of delivery of small, bioactive molecules such as chemotherapeutic drugs.
Authors: Nibedita Ghosh, Lal Mohan Kundu
Institution: Indian Institute of Technology Guwahati
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W4403707884