Engineering β-sheets employing N-methylated heterochiral amino acids.

Engineering β-sheets employing N-methylated heterochiral amino acids.
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使用N-甲基化杂色氨基酸的工程β-折叠。

DOI:
10.1039/c6sc00518g
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发表时间:
2016-08-01
期刊:
影响因子:
8.4
通讯作者:
Chatterjee J
Chatterjee J
中科院分区:
化学1区
文献类型:
--
作者:
Ghosh D;Lahiri P;Verma H;Mukherjee S;Chatterjee J

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据报道,可工程化的 β 转角基序可调节 β 片层的右旋程度。在设计的肽、蛋白质和折叠体中,成核 β-折叠构象的反转基序缺乏功能组多样性。这些序列大部分由 d-Pro-l-Pro、d-Pro-Gly 或 Asn-Gly 组成,作为转角诱导基序,限制了它们的生物学应用和物理化学调节。在本报告中,我们首次阐明线性肽中异手性氨基酸的 N-甲基化使 β-折叠构象成核,而无需在反向转弯处具有环或共价约束。我们的结果表明,d-Pro 可以方便地被任何其他 N-甲基化 d-氨基酸取代,然后被 N-甲基化 L-氨基酸或肌氨酸取代,以采用诱导 β-折叠折叠的 βII' 转角。此外,我们还发现,反转的 i+1 或 i+2 位点上的单个氨基酸可以调节右旋,最终决定 β-发夹的折叠程度。
Engineerable β-turn motif is reported that modulates the extent of right-handed twist in β-sheets. There is a lack of functional group diversity in the reverse turn motifs nucleating a β-sheet conformation in designed peptides, proteins and foldamers. The majority of these sequences consist of d-Pro–l-Pro, d-Pro–Gly or Asn–Gly as the turn inducing motif restricting their biological application and physicochemical modulation. In this report, for the first time we elucidate that N-methylation of heterochiral amino acids in linear peptides nucleates β-sheet conformation without the necessity of having a ring or covalent constraint at the reverse turn. Our results show that d-Pro can be conveniently substituted by any other N-methylated d-amino acid followed by an N-methylated l-amino acid or sarcosine to adopt a βII′ turn inducing the β-sheet folding. Furthermore, we reveal that a single amino acid either at the i + 1 or i + 2 site of the reverse turn can modulate the right-handed twist, which eventually dictates the extent of the foldedness of the β-hairpin.
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