4-Fluoroprolines: Conformational Analysis and Effects on the Stability and Folding of Peptides and Proteins.
4-Fluoroprolines: Conformational Analysis and Effects on the Stability and Folding of Peptides and Proteins.
复制标题
4-氟丙烯酯：构象分析和对肽和蛋白质稳定性和折叠的影响。
DOI：
10.1007/7081_2015_196
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Raines RT
中科院分区：
文献类型：
--
作者：
Newberry RW;Raines RT
脯氨酸在蛋白质氨基酸中是独特的，因为吡咯烷环将其氨基连接到其侧链。该杂环约束主链的构象，从而模板化特定的二级结构。脯氨酸残基在4位进行翻译后修饰，产生4-羟脯氨酸，这在胶原蛋白中尤其普遍。在表征这种修饰的影响的兴趣导致使用4-氟脯氨酸，以增强相对于4-羟基脯氨酸的羟基的诱导性质，并消除氢键的贡献。氟基团的强诱导作用有三个主要后果：在吡咯烷环上强制执行特定的褶皱，使前面的肽键的构象偏向，以及加速顺式/反式脯氨酰肽键异构化。这些微妙而可靠的调节使4-氟脯氨酸掺入成为传统遗传方法的补充，用于探索肽和蛋白质的结构-功能关系，以及赋予肽和蛋白质构象稳定性。
Proline is unique among proteinogenic amino acids because a pyrrolidine ring links its amino group to its side chain. This heterocycle constrains the conformations of the main chain and thus templates particular secondary structures. Proline residues undergo post-translational modification at the 4-position to yield 4-hydroxyproline, which is especially prevalent in collagen. Interest in characterizing the effects of this modification led to the use of 4-fluoroprolines to enhance inductive properties relative to the hydroxyl group of 4-hydroxyproline and to eliminate contributions from hydrogen bonding. The strong inductive effect of the fluoro group has three main consequences: enforcing a particular pucker upon the pyrrolidine ring, biasing the conformation of the preceding peptide bond, and accelerating cis/trans prolyl peptide bond isomerization. These subtle, yet reliable modulations make 4-fluoroproline–incorporation a complement to traditional genetic approaches for exploring structure–function relationships in peptides and proteins, as well as for endowing peptides and proteins with conformational stability.