Water-Soluble Peptides with Stable Helical Structure Are Potential Nanoparticle Carriers

A paper describes the synthesis of peptides with stable helical structure that may serve as nanoparticle carriers for drug and gene delivery.

Water-soluble peptides with stable helical structure are of interest to protein chemists because of their importance in basic science and their broad utility in medicine and biotechnology. Incorporating charged amino-acid residues to improve peptide solubility, however, usually leads to reduced helical stability because of increased side-chain charge repulsion, reduced side-chain hydrophobicity, and the disruption of intramolecular hydrogen bonding.

In the current study, published in the February 22, 2011, online edition of the journal Nature Communications, investigators at the University of Illinois (Urbana-Champaign, USA) showed that water-soluble, ultra-stable alpha-helical polypeptides could be produced by elongating charge-containing amino-acid side chains to position the charges far removed from the polypeptide backbone. As the length of the side chains with charges on the end increased, the tendency of the polypeptides to form helices also increased. The helices prepared by this method displayed remarkable stability even when compared to noncharged helices and were resistant to temperature, pH, and other denaturing agents that would denature most polypeptides.

"You can achieve the helical structure and the solubility but you have to design the helical structure in a very special way. The peptide design needs a very specific sequence. Then you are very limited in the type of polypeptide you can build, and it is not easy to design or handle these polypeptides,” said senior author Dr. Jianjun Cheng, professor of materials science and engineering at the University of Illinois. "It is such a simple idea – move the charge away from the backbone. It is not difficult at all to make the longer side chains, and it has amazing properties for winding up helical structures simply by pushing the distance between the charge and the backbone.”

"We want to test the correlation of the lengths of the helices and the circulation in the body to see what is the impact of the shape and the charge and the side chains for clearance in the body,” said Dr. Cheng. "Recent studies show that the aspect ratio of the nanostructures – spherical structures versus tubes – has a huge impact on their penetration of tumor tissues and circulation half-lives in the body.”

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