Department of Physical Chemistry, University of Seville, C/ Profesor García González 1, 41012 Seville, Spain.
Department of Chemical Engineering, Physical Chemistry and Materials Science, Faculty of Experimental Sciences, Campus de El Carmen, Avda. de las Fuerzas Armadas s/n, 21071 Huelva, Spain.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110399. doi: 10.1016/j.colsurfb.2019.110399. Epub 2019 Jul 27.
The interaction between calf thymus DNA, ctDNA, and a series of oligomeric surfactants derived from N-benzyl-N,N-dimethyl-N-(1-dodecyl)ammonium chloride is investigated. The influence of the surfactants' degree of oligomerization (2, 3 and 4) on the ctDNA/surfactant interaction is studied, as well as the effect of the structure of the spacer group linking the individual surfactant fragments. In particular, the effect of the distance between the positive charges and the hydrophobic chains within the oligomers on these interactions was examined, by using the three positional isomers (i.e., ortho-, meta-, and para-) with the rigid xylidene moiety as spacer. Results show that the dimeric ("gemini") surfactants are much more efficient in the inversion of the nucleic acid charge than the single-chained (monomeric) surfactant. Whereas the ortho - isomer causes a partial condensation, the meta - and para - isomers can completely condense ctDNA. The meta - and para - isomers of the trimeric surfactants can also completely condense the polynucleotide. In contrast, the tetrameric surfactant investigated does not change the morphology of the nucleic acid from an elongated coil into a compacted form, in spite of effectively inverting the nucleic acid's charge in their complex. Accordingly, the capacity for ctDNA compaction of oligomeric surfactants is not simply correlated to their degree of oligomerization, but depends on a complex balance of the number and relative distance of cationic charges and/or hydrophobic tails in the surfactants for effectively interacting with the nucleic acid to form the appropriate complex. This information will help to design more effective cationic surfactants as non-viral vectors for gene therapy.
研究了小牛胸腺 DNA（ctDNA）与一系列源自 N-苄基-N，N-二甲基-N-（1-十二烷基）氯化铵的低聚表面活性剂之间的相互作用。研究了表面活性剂的低聚度（2、3 和 4）对 ctDNA/表面活性剂相互作用的影响，以及连接各个表面活性剂片段的间隔基的结构对该相互作用的影响。特别地，通过使用刚性二甲苯部分作为间隔基的三种位置异构体（即邻位、间位和对位），考察了在低聚物内的正电荷和疏水链之间的距离对这些相互作用的影响。结果表明，二聚体（“双子”）表面活性剂比单链（单体）表面活性剂更有效地反转核酸电荷。虽然邻位异构体导致部分缩合，但间位和对位异构体可以完全缩合 ctDNA。三聚体表面活性剂的间位和对位异构体也可以完全缩合多核苷酸。相比之下，尽管在其复合物中有效地反转了核酸的电荷，但所研究的四聚体表面活性剂并未将核酸的形态从拉长的螺旋结构改变为紧凑的形式。因此，低聚表面活性剂对 ctDNA 紧缩的能力与其低聚度并非简单相关，而是取决于表面活性剂中阳离子电荷和/或疏水尾部的数量和相对距离的复杂平衡，以便有效地与核酸相互作用形成适当的复合物。这些信息将有助于设计更有效的阳离子表面活性剂作为非病毒载体用于基因治疗。
