Vasudev Prema G, Ananda Kuppanna, Chatterjee Sunanda, Aravinda Subrayashastry, Shamala Narayanaswamy, Balaram Padmanabhan
Department of Physics, Indian Institute of Science, Bangalore-560012, India.
J Am Chem Soc. 2007 Apr 4;129(13):4039-48. doi: 10.1021/ja068910p. Epub 2007 Mar 10.
The crystal structure of 12 peptides containing the conformationally constrained 1-(aminomethyl)cyclohexaneacetic acid, gabapentin (Gpn), are reported. In all the 39 Gpn residues conformationally characterized so far, the torsion angles about the Calpha-Cbeta and Cbeta-Cgamma bonds are restricted to the gauche conformation (+/-60 degrees ). The Gpn residue is constrained to adopt folded conformations resulting in the formation of intramolecularly hydrogen-bonded structures even in short peptides. The peptides Boc-Ac6c-Gpn-OMe 1 and Boc-Gpn-Aib-Gpn-Aib-OMe 2 provide examples of C7 conformation; peptides Boc-Gpn-Aib-OH 3, Boc-Ac6c-Gpn-OH 4, Boc-Val-Pro-Gpn-OH 5, Piv-Pro-Gpn-Val-OMe 6, and Boc-Gpn-Gpn-Leu-OMe 7 provide examples of C9 conformation; peptide Boc-Ala-Aib-Gpn-Aib-Ala-OMe 8 provides an example of C12 conformation and peptides Boc-betaLeu-Gpn-Val-OMe 9 and Boc-betaPhe-Gpn-Phe-OMe 10 provide examples of C13 conformation. Gpn peptides provide examples of backbone expanded mimetics for canonical alpha-peptide turns like the gamma (C7) and the beta (C10) turns. The hybrid betagamma sequences provide an example of a mimetic of the C13 alpha-turn formed by three contiguous alpha-amino acid residues. Two examples of folded tripeptide structures, Boc-Gpn-betaPhe-Leu-OMe 11 and Boc-Aib-Gpn-betaPhg-NHMe 12, lacking internal hydrogen bonds are also presented. An analysis of available Gpn residue conformations provides the basis for future design of folded hybrid peptides.
报道了12种含有构象受限的1-(氨甲基)环己烷乙酸（加巴喷丁，Gpn）的肽的晶体结构。在迄今已进行构象表征的所有39个Gpn残基中，围绕Cα-Cβ和Cβ-Cγ键的扭转角被限制在 gauche 构象（±60°）。即使在短肽中，Gpn残基也被迫采取折叠构象，从而形成分子内氢键结构。肽Boc-Ac6c-Gpn-OMe 1和Boc-Gpn-Aib-Gpn-Aib-OMe 2提供了C7构象的例子；肽Boc-Gpn-Aib-OH 3、Boc-Ac6c-Gpn-OH 4、Boc-Val-Pro-Gpn-OH 5、Piv-Pro-Gpn-Val-OMe 6和Boc-Gpn-Gpn-Leu-OMe 7提供了C9构象的例子；肽Boc-Ala-Aib-Gpn-Aib-Ala-OMe 8提供了C12构象的例子，而肽Boc-βLeu-Gpn-Val-OMe 9和Boc-βPhe-Gpn-Phe-OMe 10提供了C13构象的例子。Gpn肽为典型α-肽转角（如γ（C7）和β（C10）转角）的主链扩展模拟物提供了实例。杂合βγ序列为三个连续α-氨基酸残基形成的C13α-转角模拟物提供了实例。还展示了两个缺乏内部氢键的折叠三肽结构实例，即Boc-Gpn-βPhe-Leu-OMe 11和Boc-Aib-Gpn-βPhg-NHMe 12。对现有Gpn残基构象的分析为未来折叠杂合肽的设计提供了基础。
