Paolino Marco, Komber Hartmut, Mennuni Laura, Caselli Gianfranco, Appelhans Dietmar, Voit Brigitte, Cappelli Andrea
Dipartimento di Biotecnologie, Chimica e Farmacia and European Research Centre for Drug Discovery and Development, Università degli Studi di Siena , Via A. Moro 2, 53100 Siena, Italy.
Biomacromolecules. 2014 Nov 10;15(11):3985-93. doi: 10.1021/bm501057d. Epub 2014 Oct 20.
Specific noncovalent interactions are commonly used by nature to modulate numerous processes including cell recognition, viral adhesion, and transmembrane communications. Here we report on the design, synthesis, and preliminary characterization of new supramolecular glycodendrimer-based hybrid drugs based on adamantyl-modified glycodendrimers of third, fourth, or fifth generation (mPPI-G3-AdaB, mPPI-G4-AdaB, and mPPI-G5-AdaB) and a new heterobifunctional ligand. This component was tailored to bind through noncovalent interactions both the multimeric natural 5-HT3 receptor (through an optimized arylpiperazine pharmacophore) and the adamantyl groups located on the glycodendrimer surfaces (through a β-cyclodextrin residue) giving rise to biorelevant supramolecular constructs.
自然界通常利用特定的非共价相互作用来调节众多过程，包括细胞识别、病毒黏附及跨膜通讯。在此，我们报道了基于第三代、第四代或第五代金刚烷基修饰的糖树状大分子（mPPI-G3-AdaB、mPPI-G4-AdaB和mPPI-G5-AdaB）以及一种新型异双功能配体的新型超分子糖树状大分子杂合药物的设计、合成及初步表征。该组分经设计可通过非共价相互作用，与多聚体天然5-HT3受体（通过优化的芳基哌嗪药效基团）和位于糖树状大分子表面的金刚烷基团（通过β-环糊精残基）结合，从而产生具有生物学相关性的超分子构建体。
