Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation

被引:66
作者
Danelius, Emma [1 ]
Andersson, Hanna [1 ]
Jarvoll, Patrik [1 ]
Lood, Kajsa [1 ]
Grafenstein, Jurgen [1 ]
Erdelyi, Mate [1 ,2 ]
机构
[1] Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden
[2] Swedish NMR Ctr, Med Aregatan 5, SE-41390 Gothenburg, Sweden
基金
瑞典研究理事会; 欧洲研究理事会;
关键词
BETA-HAIRPIN STABILITY; STRUCTURAL DETERMINANTS; MEDICINAL CHEMISTRY; AMINO-ACIDS; PROTEIN; MODEL; NMR; PROPENSITIES; RECOGNITION; MOLECULES;
D O I
10.1021/acs.biochem.7b00429
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Halogen bonding is a weak chemical force that has so far mostly found applications in crystal engineering. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a beta-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.
引用
收藏
页码:3265 / 3272
页数:8
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