Flaws in foldamers: conformational uniformity and signal decay in achiral helical peptide oligomers.
Flaws in foldamers: conformational uniformity and signal decay in achiral helical peptide oligomers.
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DOI：
10.1039/c4sc03944k
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发表时间：
2015-04-01
期刊：
影响因子：
8.4
通讯作者：
Clayden J
中科院分区：
文献类型：
--
作者：
Le Bailly BAF;Byrne L;Diemer V;Foroozandeh M;Morris GA;Clayden J
在其他非手性寡聚物中，单个立体中心的构象影响表现为随距离衰减的信号。虽然根据定义，折叠体是具有明确定义的构象的延伸分子结构，但次要构象异构体必须在溶液中至少在一定程度上被填充。我们提出了一个定量分析的这些次要构象的一系列螺旋低聚物的非手性，但螺旋α-氨基酸。通过测量链长依赖性或链位置依赖性的NMR或CD量，测量螺旋感偏好的螺旋低聚物，我们量化的构象信号的衰减常数的值，因为它通过分子结构。这种构象信号是M和P螺旋的外消旋混合物的扰动，这类低聚物通常通过包含N或C末端手性诱导剂而采用。我们表明，衰减常数可能是非常低的（<1%的信号损失每个残基）在非极性溶剂中，我们评估的衰减常数的增加，导致极性溶剂中，在较高的温度下，和更多的构象灵活的残基，如甘氨酸。衰减常数与信号是来自N端还是C端无关。通过解释的衰变常数的概率，其中包含一个螺旋感反转的构象填充，我们量化的人口这些替代的次要构象内的整体合奏的二级结构所采用的折叠体。我们推导出AIB聚合物的螺旋持久长度，使我们能够表明，在非极性溶剂中的肽螺旋，即使在没有手性残基的情况下，可以继续与相同的螺旋意义约200个残基。
The conformational influence of a single stereogenic centre in an otherwise achiral oligomer behaves as a signal that decays with distance. Although foldamers, by definition, are extended molecular structures with a well-defined conformation, minor conformers must be populated at least to some extent in solution. We present a quantitative analysis of these minor conformers for a series of helical oligomers built from achiral but helicogenic α-amino acids. By measuring the chain length dependence or chain position dependence of NMR or CD quantities that measure screw-sense preference in a helical oligomer, we quantify values for the decay constant of a conformational signal as it passes through the molecular structure. This conformational signal is a perturbation of the racemic mixture of M and P helices that such oligomers typically adopt by the inclusion of an N or C terminal chiral inducer. We show that decay constants may be very low (<1% signal loss per residue) in non-polar solvents, and we evaluate the increase in decay constant that results in polar solvents, at higher temperatures, and with more conformationally flexible residues such as Gly. Decay constants are independent of whether the signal originates from the N or the C terminus. By interpreting the decay constant in terms of the probability with which conformations containing a screw-sense reversal are populated, we quantify the populations of these alternative minor conformers within the overall ensemble of secondary structures adopted by the foldamer. We deduce helical persistence lengths for Aib polymers that allow us to show that in a non-polar solvent a peptide helix, even in the absence of chiral residues, may continue with the same screw sense for approximately 200 residues.
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影响因子：
16.6
作者：
Foroozandeh, Mohammadali;Adams, Ralph W.;Meharry, Nicola J.;Jeannerat, Damien;Nilsson, Mathias;Morris, Gareth A.
通讯作者：
Morris, Gareth A.
影响因子：
56.9
作者：
DICKERSON, RE;DREW, HR;KOPKA, ML
通讯作者：
KOPKA, ML
影响因子：
16.6
作者：
Clayden, Jonathan;Castellanos, Alejandro;Morris, Gareth A.
通讯作者：
Morris, Gareth A.
影响因子：
6.2
作者：
Inai, Y;Komori, H
通讯作者：
Komori, H
影响因子：
15
作者：
Foroozandeh, Mohammadali;Adams, Ralph W.;Morris, Gareth A.
通讯作者：
Morris, Gareth A.