NMR determination of the major solution conformation of a peptoid pentamer with chiral side chains
NMR determination of the major solution conformation of a peptoid pentamer with chiral side chains
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DOI：
10.1073/pnas.95.8.4309
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发表时间：
1998-04-14
影响因子：
11.1
通讯作者：
Bradley, EK
中科院分区：
文献类型：
--
作者：
Armand, P;Kirshenbaum, K;Bradley, EK
侧链上含有手性中心的N-取代甘氨酸(“类肽”)聚合物在溶液中可以形成稳定的结构。我们用核磁共振波谱研究了一个由五个对取代的(S)-N-(1-苯乙基)甘氨酸残基组成的原型类肽。观察到了多个构型异构体，但由于信号的广泛重叠，只对包含所有顺酰胺键的主要异构体进行了详细研究。该分子的核磁共振数据结合以前的CD光谱结果表明，甲醇中的主要物种是带有顺酰胺键的右旋螺旋。螺旋的周期为每转三个残基，螺距约为6埃。这种构象类似于手性类肽八聚体的计算研究所预期的构象。螺旋重复序列以与该分子表现出的CD信号的强度一致的方式来定向酰胺键发色团。许多其他手性多肽具有类似的CD光谱，这表明含有手性侧链的整个类肽家族都能够采用这个二级结构基序。综上所述，我们对手性类肽分子结构性质的实验和理论研究为合理设计更复杂的多肽分子奠定了基础，并具有从纳米结构到非病毒基因递送系统的各种应用。
Polymers of N-substituted glycines ("peptoids") containing chiral centers at the a position of their side chains can form stable structures in solution. We studied a prototypical peptoid, consisting of five para substituted (S)-N-(1-phenylethyl)glycine residues, by NMR spectroscopy. Multiple configurational isomers were observed, but because of extensive signal overlap, only the major isomer containing all cis-amide bonds was examined in detail. The NMR data for this molecule, in conjunction with previous CD spectroscopic results, indicate that the major species in methanol is a right-handed helix with cis-amide bonds. The periodicity of the helix is three residues per turn, with a pitch of approximate to 6 Angstrom. This conformation is similar to that anticipated by computational studies of a chiral peptoid octamer. The helical repeat orients the amide bond chromophores in a manner consistent with the intensity of the CD signal exhibited by this molecule. Many other chiral polypeptoids have similar CD spectra, suggesting that a whole family of peptoids containing chiral side chains is capable of adopting this secondary structure motif. Taken together, our experimental and theoretical studies of the structural properties of chiral peptoids lay the groundwork for the rational design of more complex polypeptoid molecules, with a variety of applications, ranging from nanostructures to nonviral gene delivery systems.