Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
MTA-ELTE Protein Modelling Research Group, Pázmány P. stny. 1/A, Budapest, 1117, Hungary.
Chemistry. 2020 Sep 4;26(50):11643-11655. doi: 10.1002/chem.202000882. Epub 2020 Aug 10.
The configuration-dependent self-association mode of the two anomers of O-Ac,N-Fmoc-d-glucosamine, a foldamer building block, leading to gel and/or single crystal formation is described. The β-anomer of the sugar amino acid (2) forms a gel from various solvents (confirmed by SEM, rheology measurements, NMR, and ECD spectroscopy), whereas the α-anomer (1) does not form a gel with any solvent tested. Transition from the solution state to a gel is coupled to a concurrent shift of the Fmoc-groups: from a freely rotating (almost symmetrical) to a specific, asymmetric orientation. Whereas the crystal structure of the α-anomer is built as an evenly packed 3D system, the β-anomer forms a looser superstructure of well-packed 2D layers. Modeling indicates that in the lowest energy, but scarcely sampled conformer of the β-anomer, the Fmoc-group bends above the sugar moiety, stabilized by intramolecular CH↔π interactions between the aromatic rings. It is concluded that possessing an extended and promiscuous interaction surface and a conformationally heterogeneous solution state are among the basic requirements of gel formation for a candidate molecule.
描述了作为折叠物构建块的 O-Ac，N-Fmoc-d-葡萄糖胺的两种差向异构体的、依赖于构型的自缔合模式，导致凝胶和/或单晶形成。糖氨基酸的β-差向异构体（2）可从各种溶剂中形成凝胶（通过 SEM、流变学测量、NMR 和 ECD 光谱证实），而α-差向异构体（1）与测试的任何溶剂均不形成凝胶。从溶液状态向凝胶状态的转变与 Fmoc 基团的同时迁移相关：从自由旋转（几乎对称）到特定的、不对称的方向。尽管α-差向异构体的晶体结构构建为均匀堆积的 3D 系统，但β-差向异构体形成了堆积良好的 2D 层的较松散的超结构。建模表明，在β-差向异构体的最低能量但几乎未采样构象中，Fmoc 基团在糖部分上方弯曲，由芳环之间的分子内 CH↔π 相互作用稳定。可以得出结论，具有扩展的、混杂的相互作用表面和构象异质的溶液状态是候选分子形成凝胶的基本要求之一。
