Newberry Robert W, Raines Ronald T
Departments of Chemistry and Biochemistry, University of Wisconsin-Madison, Madison, WI 53706 USA.
Top Heterocycl Chem. 2017;48:1-25. doi: 10.1007/7081_2015_196. Epub 2016 Jan 12.
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 / 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.
脯氨酸在蛋白质ogenic氨基酸中是独特的，因为一个吡咯烷环将其氨基连接到其侧链。这种杂环限制了主链的构象，从而形成特定的二级结构模板。脯氨酸残基在4位进行翻译后修饰，生成4-羟基脯氨酸，这在胶原蛋白中尤为普遍。对表征这种修饰效果的兴趣导致使用4-氟脯氨酸来增强相对于4-羟基脯氨酸羟基的诱导特性，并消除氢键的贡献。氟基团的强诱导效应有三个主要后果：使吡咯烷环形成特定的褶皱，使前一个肽键的构象产生偏差，以及加速脯氨酰肽键异构化。这些微妙而可靠的调节使得掺入4-氟脯氨酸成为探索肽和蛋白质结构-功能关系的传统遗传方法的补充，以及赋予肽和蛋白质构象稳定性。
