A new turn structure for the formation of β-hairpins in peptides
A new turn structure for the formation of β-hairpins in peptides
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DOI：
10.1021/ja028938a
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发表时间：
2003-01-29
影响因子：
15
通讯作者：
Brower, JO
中科院分区：
文献类型：
--
作者：
Nowick, JS;Brower, JO
盖尔曼和他的同事之前的研究已经优雅地表明，基于镜像peptide1[Arg-Trp-Gln-Tyr-Val-d-Pro-Gly-Lys-Phe-Thr-Val-Gln-NH2]-β-Turns的upond-Pro-Gly特别擅长稳定β-发夹，并证明了β折叠成一个定义明确的Uond-发夹[Espinosa，J.F.；Gellman，S.H.Angew。Int.Chem.，Int.2000，39,2330−2333版]。本研究证实了氨基酸鸟氨酸(Orn)也形成了一个转弯结构，当通过β-氨基连接时，该转弯结构具有良好的稳定δ-发夹的作用，并且在诱导β-发夹形成的能力上与D-Pro-Gly相当。因此，1H核磁共振化学位移和NOE研究证实，含Orn的analogue2[Arg-Trp-Gln-Tyr-Val-δOrn-Lys-Phe-Thr-Val-Gln-NH2]在结构上与肽1相似。本研究还证实了Orn旋转优于Asn-Gly旋转，并且用δOrder-εOrn替换δOrn产生的结构不会明显折叠。
Previous studies by Gellman and co-workers have elegantly shown that mirror-image β-turns based upond-Pro-Gly are especially good at stabilizing β-hairpins and have demonstrated that peptide1[Arg-Trp-Gln-Tyr-Val-d-Pro-Gly-Lys-Phe-Thr-Val-Gln-NH2] folds into a well-defined β-hairpin [Espinosa, J. F.; Gellman, S. H.Angew. Chem., Int. Ed.2000,39, 2330−2333]. The present study establishes that the amino acid ornithine (Orn) also forms a turn structure that is excellent at stabilizing β-hairpins when linked through the δ-amino group and that this turn is comparable tod-Pro-Gly in ability to induce β-hairpin formation. Thus,1H NMR chemical shift and NOE studies establish that Orn-containing analogue2[Arg-Trp-Gln-Tyr-Val-δOrn-Lys-Phe-Thr-Val-Gln-NH2] is comparable in structure to peptide1. The present study also establishes that the Orn turn is superior to Asn-Gly turns and that replacement of theδOrn withεLys ord-δOrn generates structures that do not fold significantly.