Departament de Química, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
Org Biomol Chem. 2010 Feb 7;8(3):564-75. doi: 10.1039/b918755c. Epub 2009 Dec 3.
Improved methodologies are provided to synthesize (1R,2S)-2-aminocyclobutane-1-carboxylic acid derivatives and their incorporation into beta-peptides of 2-8 residues bearing different N-protecting groups. The conformational analysis of these oligomers has been carried out by using experimental techniques along with theoretical calculations. This study shows that these oligomers adopt preferentially a strand-type conformation in solution induced by the formation of intra-residue six-membered hydrogen-bonded rings, affording cis-fused [4.2.0]octane structural units that confer high rigidity on these beta-peptides. Moreover, all of them are prone to self-assemble producing nano-sized fibres, as evidenced by TEM, AFM and SPFM, and, in some instances, they also form gels. These techniques and molecular modelling allowed us to suggest an aggregation model for the assembly structures in which a parallel molecular-arrangement is preferred and the conformation is similar to that observed in solution. According to this model, both hydrogen-bonding and hydrophobic interactions would account for formation of the assemblies.
提供了改进的方法来合成（1R,2S）-2-氨基环丁烷-1-羧酸衍生物，并将其并入具有不同 N-保护基团的 2-8 个残基的β-肽中。通过使用实验技术和理论计算对这些低聚物进行了构象分析。这项研究表明，这些低聚物在溶液中优先采用由形成内残基六元氢键环诱导的链型构象，提供顺式稠合的[4.2.0]辛烷结构单元，赋予这些β-肽高刚性。此外，它们都易于自组装产生纳米尺寸的纤维，这可以通过 TEM、AFM 和 SPFM 证明，并且在某些情况下，它们还形成凝胶。这些技术和分子建模使我们能够提出一种聚集模型，用于组装结构，其中优先采用平行的分子排列，构象类似于在溶液中观察到的构象。根据该模型，氢键和疏水相互作用都可以解释组装的形成。
