Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length

Abstract

Amine containing polymers are extensively studied as special carriers for short-chain RNA (13–25 nucleotides), which are applied as gene silencing agents in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of the oligonucleotide–polymeric amine interaction. The critical length of the interacting chains is an important parameter which allows us to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interactions of (TCAG)n, n = 1–6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethylamino)propyl)(methyl)amino)propyl)-N-methylacrylamide). The critical length for oligonucleotides in interaction with polymeric amines is 8–12 units and complexation at these length can be accompanied by “all-or-nothing” effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells and silencing efficiency against vascular endothelial growth factor (VEGF) was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e., for a sample in which all grafted chains are longer than the critical length for polymeric amine–oligonucleotide complexation.

Acrylamide derivatives: A dynamic nuclear magnetic resonance study

“…The second, less stable, skew conformer was found to be nonplanar with the dihedral angle of about 155 between C=O and C=C fragments. Quantum-chemical calculations carried out in the work [9] at the B3LYP/cc-pVTZ level of theory confirmed the structures of both conformers and showed good agreement with the experimental data. Studies of the IR spectra of acrylamide [9,10] have also indicated that acrylamide has a planar amide group with the most stable syn arrangement.…”

“…Quantum-chemical calculations carried out in the work [9] at the B3LYP/cc-pVTZ level of theory confirmed the structures of both conformers and showed good agreement with the experimental data. Studies of the IR spectra of acrylamide [9,10] have also indicated that acrylamide has a planar amide group with the most stable syn arrangement. However, the ab initio calculations carried out at the MP2/6-31G* level by Lin et al [11] were not conclusive concerning the planarity of the amide group.…”

“…[ 7,8 ] Thus, interest in this class of compounds is constantly growing, as evidenced by the large number of publications devoted to the chemistry and biological aspects of acrylamide derivatives. [ 9 ] Such a wide use of functionalized acrylamides requires an understanding of their electronic structure peculiarities, spectral properties, reactivity, and synthetic approaches.…”

“…Systematic research in this area was not carried out, although some facts about the presence of rotational isomerism in acrylamide derivatives are reported. [10][11][12][13][14] In particular, the microwave spectrum of the acrylamide (CH 2 = CH-CONH 2 ) was recorded [9] in the 20.0-to 60.5-GHz spectral region at the room temperature, and it was found that acrylamide exists as two conformers with the most stable planar rotamer, in which the carbonyl and vinyl groups are in the syn arrangement…”