Menzi Mirjam, Lightfoot Helen L, Hall Jonathan
Department of Chemistry & Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland.
Future Med Chem. 2015;7(13):1733-49. doi: 10.4155/fmc.15.90. Epub 2015 Oct 1.
Chemical modification and/or the conjugation of small functional molecules to oligonucleotides have significantly improved their biological and biophysical properties, addressing issues such as poor cell penetration, stability to nucleases and low affinity for their targets. Here, the authors review the literature reporting on the biophysical, biochemical and biological properties of one particular class of modification - polyamine-oligonucleotide conjugates. Naturally derived and synthetic polyamines have been grafted onto a variety of oligonucleotide formats, including antisense oligonucleotides and siRNAs. In many cases this has had beneficial effects on their properties such as target hybridization, nuclease resistance, cellular uptake and activity. Polyamine-oligonucleotide conjugation, therefore, represents a promising direction for the further development of oligonucleotide-based therapeutics and tools.
小分子功能分子与寡核苷酸的化学修饰和/或缀合显著改善了它们的生物学和生物物理性质，解决了诸如细胞穿透性差、对核酸酶的稳定性以及对其靶标的低亲和力等问题。在此，作者回顾了关于一类特定修饰——聚胺-寡核苷酸缀合物的生物物理、生化和生物学性质的文献报道。天然衍生的和合成的聚胺已被嫁接到多种寡核苷酸形式上，包括反义寡核苷酸和小干扰RNA。在许多情况下，这对它们的性质如靶标杂交、核酸酶抗性、细胞摄取和活性产生了有益影响。因此，聚胺-寡核苷酸缀合代表了基于寡核苷酸的治疗剂和工具进一步发展的一个有前景的方向。
