Portal de Periódicos da CAPES

Ionic polypeptides with unusual helical stability

2011; Nature Portfolio; Volume: 2; Issue: 1 Linguagem: Inglês

10.1038/ncomms1209

2041-1723

Hua Lu, Jing Wang, Yugang Bai, Jason W. Lang, Shiyong Liu, Yao Lin, Jianjun Cheng,

Antimicrobial Peptides and Activities

Water-soluble peptides that adopt stable helical conformations are attractive motifs 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. Here, we show that water-soluble, ultra-stable α-helical polypeptides can be produced by elongating charge-containing amino-acid side chains to position the charges distally from the polypeptide backbone. The strategy has been successfully applied to the design and synthesis of water-soluble polypeptides bearing long, charged side chains and various functional moieties that possess unusual helical stability against changing environmental conditions, including changes in the pH and temperature and the presence of denaturing reagents. Water-soluble peptides with stable α-helical conformations are desirable for a range of applications, but incorporating charged residues to improve solubility usually leads to reduced helical stability. Here, polypeptides produced from amino acids with elongated charged side chains are found to be water soluble and exhibit very high helical stability.