scholarly journals Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

2021 ◽  
Vol 17 ◽  
pp. 908-931
Author(s):  
Christopher Liczner ◽  
Kieran Duke ◽  
Gabrielle Juneau ◽  
Martin Egli ◽  
Christopher J Wilds

Over the past 25 years, the acceleration of achievements in the development of oligonucleotide-based therapeutics has resulted in numerous new drugs making it to the market for the treatment of various diseases. Oligonucleotides with alterations to their scaffold, prepared with modified nucleosides and solid-phase synthesis, have yielded molecules with interesting biophysical properties that bind to their targets and are tolerated by the cellular machinery to elicit a therapeutic outcome. Structural techniques, such as crystallography, have provided insights to rationalize numerous properties including binding affinity, nuclease stability, and trends observed in the gene silencing. In this review, we discuss the chemistry, biophysical, and structural properties of a number of chemically modified oligonucleotides that have been explored for gene silencing.

2014 ◽  
Vol 908 ◽  
pp. 215-219 ◽  
Author(s):  
Li Ying Mo ◽  
Yan Ling Wu ◽  
Min Rui Liu ◽  
Xing Lai Chen ◽  
Yan Ping Ding ◽  
...  

Over the past years, synthesis of pyrrole-imidazole (Py-Im) polyamides has been achieved by solution-phase and solid-phase methods. Comparing with solution-phase synthesis, the solid-phase synthesis has showed great superiority in various aspects. The solid-phase synthesis is a rapid, effective, energy-saving and environment-friendly method, which has been widely used in the synthesis of pyrrole-imidazole polyamides. Many complicated polyamides can be obtained quickly and effectively through this method. By far, the application of the solid-phase synthesis for Py-Im polyamides has made rapid development. Resin as the main carrier, a key substance in solid phase synthesis, consists of two parts: polymer (macromolecular resin) and linking chain (linker). To date, there are many kinds of resins applied in the solid phase synthesis, such as PAM resin, Wang resin, Oxime resin and Clear resin, and so on. In this article, we will focus on the elaboration about the basic principle and application of the four kinds of resins mentioned above in solid-phase synthesis of polyamides. This provides an important reference for development of polyamides.


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