The helix-destabilizing propensity scale of D-amino acids: The influence of side chain steric effects
The helix-destabilizing propensity scale of D-amino acids: The influence of side chain steric effects
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DOI：
10.1021/ja9940524
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发表时间：
2000-05-24
影响因子：
15
通讯作者：
Wenschuh, H
中科院分区：
文献类型：
--
作者：
Krause, E;Bienert, M;Wenschuh, H
尽管 D-氨基酸存在于各种天然存在的肽中，并且经常用于结构活性研究，但人们对其对 L-氨基酸形成的螺旋二级结构的影响知之甚少。尽管之前的一些报道报道了 L-氨基酸的 α-螺旋倾向，但目前的贡献首次针对所有蛋白质氨基酸的相应 D-对映体解决了这个问题。因此，通过圆二色性 (CD) 光谱、核磁共振和反相 HPLC 评估了宿主序列乙酰基-KLALKLALxxLKLALKLA-酰胺 (x(9,10)-KLA) 中 19 个 D-氨基酸的螺旋不稳定能力。 CD 和 HPLC 数据能够计算 D-氨基酸 x 相对于甘氨酸 (Delta Delta G(t)) 或相应的 L-氨基酸 (Delta Delta G(D-L)) 的螺旋形成自由能的差异。数据表明，螺旋不稳定倾向高度依赖于氨基酸侧链，与相应L-氨基酸的结构倾向无关。因此，D-氨基酸可分为 (i) 弱螺旋去稳定剂（D-His、D-Asp、D-Glu、D-Cys、D-Gln、D-Asn、D-Ser）、(ii) 中等螺旋去稳定剂（D-Leu、D-Arg、D-Met、D-Lys、D-Trp、D-Ala）和 (iii) 强螺旋不稳定因素 (D-Thr、D-Phe、D-Val、D-Ile、D-Tyr、D-Pro)。因此，大体积和β-支链氨基酸的D-异构体通过诱导转角结构来破坏两亲性KLA-螺旋的稳定性是最有效的。这种 D-异构体以类似于 L-脯氨酸的方式破坏二级结构。
Although D-amino acids are found in various naturally occurring peptides and frequently used for structure-activity studies, not much is known about their impact on the helical secondary structures formed by L-amino acids. Although several previous accounts reported on the alpha-helical propensity of L-amino acids, the present contribution addresses this subject for the first time for the corresponding D-enantiomers of all of the proteinogenic amino acids. Thus, the helix-destabilizing abilities of the 19 D-amino acids in the host sequence acetyl-KLALKLALxxLKLALKLA-amide (x(9,10)-KLA) were evaluated by means of circular dichroism (CD) spectroscopy, nuclear magnetic resonance, and reversed-phase HPLC. CD and HPLC data enabled calculation of differences in the free energy of helix formation for D-amino acid x relative to glycine (Delta Delta G(t)) or to the corresponding L-amino acid (Delta Delta G(D-L)). The data show that the helix-destabilizing propensity is highly dependent on the amino acid side chain and not related to the structure propensity of the corresponding L-amino acid. In consequence, the D-amino acids can be grouped into (i) weak helix destabilizers (D-His, D-Asp, D-Glu, D-Cys, D-Gln, D-Asn, D-Ser), (ii) medium helix destabilizers (D-Leu, D-Arg, D-Met, D-Lys, D-Trp, D-Ala), and (iii) strong helix destabilizers (D-Thr, D-Phe, D-Val, D-Ile, D-Tyr, D-Pro). Accordingly, the D-isomers of bulky and beta-branched amino acids are the most effective in destabilizing the amphipathic KLA-helix by induction of turn-like structures. Such D-isomers disrupt the secondary structure in a manner similar to that of L-proline.