Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Nat Commun. 2011 Feb 22;2:206. doi: 10.1038/ncomms1209.
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.
采用稳定螺旋构象的水溶性肽因其在基础科学中的重要性及其在医学和生物技术中的广泛应用而备受关注。然而，引入带电荷的氨基酸残基以提高肽的水溶性通常会导致螺旋稳定性降低，这是由于增加了侧链电荷排斥、降低了侧链疏水性以及破坏了分子内氢键。在这里，我们表明通过延长带电荷的氨基酸侧链，可以将电荷置于多肽主链的远端，从而产生水溶性、超稳定的α-螺旋多肽。该策略已成功应用于设计和合成带有长带电荷侧链和各种功能部分的水溶性多肽，这些多肽具有对环境条件变化（包括 pH 值和温度变化以及变性试剂存在）的不寻常的螺旋稳定性。
