Del Secco Benedetta, Malachin Giulia, Milli Lorenzo, Zanna Nicola, Papini Emanuele, Cornia Andrea, Tavano Regina, Tomasini Claudia
Dipartimento di Chimica Ciamician, Alma Mater Studiorum Università di Bologna, Via Selmi 2, 40126, Bologna, Italy.
Dipartimento di Scienze Biomediche, Università di Padova, Viale G. Colombo 3, 35121, Padova, Italy.
ChemMedChem. 2017 Feb 20;12(4):337-345. doi: 10.1002/cmdc.201600597. Epub 2017 Jan 19.
Some hybrid foldamers of various length, all containing the (4R,5S)-4-carboxy-5-methyloxazolidin-2-one (d-Oxd) moiety alternating with an l-amino acid (l-Val, l-Lys, or l-Ala), were prepared in order to study their preferred conformations and to evaluate their biological activity. Surprisingly, only the longer oligomers containing l-Ala fold into well-established helices, whereas all the other oligomers give partially unfolded turn structures. Nevertheless, they all show good biocompatibility, with no detrimental effects up to 64 μm. After equipping some selected foldamers with the fluorescent tag rhodamine B, a quantitative analysis was performed by dose- and time-response fluorescence-activated cell sorting (FACS) assays with human HeLa cells and primary blood lymphocytes, granulocytes, and monocytes. Among the cell types analyzed, the oligomers associated with monocytes and granulocytes with greatest efficacy, still visible after 24 h incubation. This effect is even more pronounced for foldamers that are able to form stable helices.
制备了一些不同长度的杂合折叠体，它们都含有(4R,5S)-4-羧基-5-甲基恶唑烷-2-酮(d-Oxd)部分，并与L-氨基酸(L-缬氨酸、L-赖氨酸或L-丙氨酸)交替排列，以研究它们的优选构象并评估其生物活性。令人惊讶的是，只有含有L-丙氨酸的较长寡聚物折叠成成熟的螺旋结构，而所有其他寡聚物都呈现部分展开的转角结构。然而，它们都表现出良好的生物相容性，在高达64μm的浓度下没有有害影响。在用荧光标签罗丹明B修饰一些选定的折叠体后，通过对人HeLa细胞以及原代血淋巴细胞、粒细胞和单核细胞进行剂量和时间响应荧光激活细胞分选(FACS)分析进行了定量分析。在所分析的细胞类型中，寡聚物与单核细胞和粒细胞的结合效率最高，在孵育24小时后仍可见。对于能够形成稳定螺旋的折叠体，这种效果更为明显。
