Banaś Karolina, Lenartowicz Paweł, Staś-Bobis Monika, Dziuk Błażej, Siodłak Dawid
Faculty of Chemistry and Pharmacy, University of Opole, Oleska 48, 45-052 Opole, Poland.
Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
Int J Mol Sci. 2025 Jan 2;26(1):340. doi: 10.3390/ijms26010340.
O-Methyldehydroserine, ΔSer(Me), is a non-standard α,β-dehydroamino acid, which occurs naturally in Cyrmenins with potential pharmaceutical application. The C-terminal part and the side chain of the ΔSer(Me) residue constitute the β-methoxyacrylate unit, responsible for antifungal activity of Cyrmenins. The short model, Ac-ΔSer(Me)-OMe, was analyzed considering the geometrical isomer Z () and E (). The Ramachandran diagrams were created for both isomers, using quantum chemical calculations, to show possible conformations for isolated molecules (in vacuo), in weakly polar (chloroform) and polar (water) environments. The Ac-()-ΔSer(Me)-OMe () was synthesized and the single-crystal X-ray diffraction analysis together with FT-IR spectra were performed. The detailed analysis of the conformations of the ()-ΔSer(Me) residue is presented considering the intra- and intermolecular interactions as well as their influence on the β-methoxyacrylate part. It is concluded that the β-methoxyacrylate structural motif is able to maintain a planar geometry, crucial for biological activity, regardless of the conformation adopted by O-methyldehydroserine.
O-甲基脱氢丝氨酸（ΔSer(Me)）是一种非标准的α,β-脱氢氨基酸，天然存在于具有潜在药物应用价值的环霉素中。ΔSer(Me)残基的C末端部分和侧链构成了β-甲氧基丙烯酸酯单元，该单元负责环霉素的抗真菌活性。对短模型Ac-ΔSer(Me)-OMe，考虑了几何异构体Z（ ）和E（ ）进行了分析。利用量子化学计算为两种异构体绘制了拉马钱德兰图，以展示孤立分子（在真空中）、弱极性（氯仿）和极性（水）环境中的可能构象。合成了Ac-( )-ΔSer(Me)-OMe( )，并进行了单晶X射线衍射分析和傅里叶变换红外光谱分析。考虑分子内和分子间相互作用及其对β-甲氧基丙烯酸酯部分的影响，对( )-ΔSer(Me)残基的构象进行了详细分析。得出的结论是，无论O-甲基脱氢丝氨酸采取何种构象，β-甲氧基丙烯酸酯结构基序都能够保持对生物活性至关重要的平面几何形状。
