Sansone Francesco, Dudic Miroslav, Donofrio Gaetano, Rivetti Claudio, Baldini Laura, Casnati Alessandro, Cellai Sara, Ungaro Rocco
Dipartimento di Chimica Organica e Industriale, Università degli Studi, Viale G. P. Usberti 17/A, 43100 Parma, Italy.
J Am Chem Soc. 2006 Nov 15;128(45):14528-36. doi: 10.1021/ja0634425.
Calix[n]arenes functionalized with guanidinium groups at the upper rim and alkyl chains at the lower rim bind to DNA, condense it, and in some cases, promote cell transfection depending on their structure and lipophilicity. Atomic force microscopy (AFM) studies indicate that upon DNA binding the hydrophobic association of the lipophilic chains of cone guanidinium calix[4]arenes drives the formation of intramolecular DNA condensates, characterized by DNA loops emerging from a dense core. Furthermore, hexyl and octyl chains confer to these calixarenes cell transfection capabilities. Conversely, larger and conformationally mobile calix[6]- and calix[8]arene methoxy derivatives form intermolecular aggregates characterized by "gorgonlike" structures composed of multiple plectomenes. These adducts, in which interstrand connections are dominated by electrostatic interactions, fail to promote cell transfection. Finally, calix[4]arenes in a 1,3-alternate conformation show an intermediate behavior because they condense DNA, but the process is driven by charge-charge interactions.
上缘带有胍基、下缘带有烷基链的杯[n]芳烃会与DNA结合、使其凝聚，在某些情况下，还会根据其结构和亲脂性促进细胞转染。原子力显微镜（AFM）研究表明，在与DNA结合时，锥形胍基杯[4]芳烃的亲脂链之间的疏水缔合驱动了分子内DNA凝聚物的形成，其特征是从致密核心伸出DNA环。此外，己基和辛基链赋予这些杯芳烃细胞转染能力。相反，更大且构象可移动的杯[6]芳烃和杯[8]芳烃甲氧基衍生物形成分子间聚集体，其特征为由多个扭缠螺旋组成的“蛇发女怪样”结构。这些加合物中，链间连接以静电相互作用为主导，无法促进细胞转染。最后，呈1,3-交替构象的杯[4]芳烃表现出中间行为，因为它们能凝聚DNA，但该过程由电荷-电荷相互作用驱动。
