Razzano Vincenzo, Paolino Marco, Reale Annalisa, Giuliani Germano, Donati Alessandro, Giorgi Gianluca, Artusi Roberto, Caselli Gianfranco, Visintin Michela, Makovec Francesco, Battiato Salvatore, Samperi Filippo, Villafiorita-Monteleone Francesca, Botta Chiara, Cappelli Andrea
Dipartimento di Biotecnologie, Chimica e Farmacia, European Research Centre for Drug Discovery and Development, Università di Siena Via A. Moro 2 53100 Siena Italy
Rottapharm Biotech S.p.A. Via Valosa di Sopra 9 20900 Monza Italy
RSC Adv. 2018 Feb 26;8(16):8638-8656. doi: 10.1039/c8ra00315g. eCollection 2018 Feb 23.
A small series of Morita-Baylis-Hillman adduct (MBHA) derivatives was synthesized and made to react with imidazole, -acetylhistidine, and -acetylhexahistidine as models of poly-histidine derivatives. Intriguingly, the reaction of MBHA derivatives 1a and b with imidazole in acetonitrile-phosphate buffered saline (PBS) gave the imidazolium salt biadducts 3a and b as the main reaction products. These results were confirmed by experiments performed with -acetylhistidine and 1b and suggested the possible occurrence of these structures in the products of poly-histidine labeling with MBHA derivatives 1a and b. These compounds were then transformed into the corresponding water-soluble derivatives 1c-e by introducing oligo(ethylene glycol) chains and their reactivity was evaluated in preliminary experiments with imidazole and then with -acetylhexahistidine in PBS. The structure of polymeric materials Ac-His-6-MBHA-1d and Ac-His-6-MBHA-1e obtained using ten-fold excesses of compounds 1d and e was investigated using mass spectrometry, NMR spectroscopy, and photophysical studies, which suggested the presence of biadduct residues in both polymeric materials. These results provide the basis for the preparation of fishbone-like polymer brushes, the characterization of their properties, and the exploration of their potential applications in different fields of science such as fluorogenic labeling, fluorescence microscopy, protein PEGylation, up to the production of smart materials and biosensors.
合成了一小系列的森田-贝利斯-希尔曼加合物（MBHA）衍生物，并使其与咪唑、N-乙酰组氨酸和N-乙酰六组氨酸反应，作为多组氨酸衍生物的模型。有趣的是，MBHA衍生物1a和b在乙腈-磷酸盐缓冲盐水（PBS）中与咪唑反应，得到咪唑鎓盐双加合物3a和b作为主要反应产物。用N-乙酰组氨酸和1b进行的实验证实了这些结果，并表明在MBHA衍生物1a和b进行多组氨酸标记的产物中可能存在这些结构。然后通过引入聚乙二醇链将这些化合物转化为相应的水溶性衍生物1c - e，并在初步实验中用咪唑，然后在PBS中用N-乙酰六组氨酸评估它们的反应活性。使用质谱、核磁共振光谱和光物理研究对使用十倍过量的化合物1d和e获得的聚合物材料Ac-His-6-MBHA-1d和Ac-His-6-MBHA-1e的结构进行了研究，结果表明两种聚合物材料中都存在双加合物残基。这些结果为鱼骨状聚合物刷的制备、其性能表征以及探索它们在不同科学领域的潜在应用提供了基础，这些领域包括荧光标记、荧光显微镜、蛋白质聚乙二醇化，直至智能材料和生物传感器的生产。
