title: Advances in chemical synthesis of structurally modified bioactive RNAs.
abstract: Methods for the chemical synthesis of RNA have been available for almost half century, and presently, RNA could be chemically synthesized by automated synthesizers, using protected ribonucleosides preactivated as phosphoramidites, which has already been covered by many reviews. In addition to advancement on synthetic methods, a variety of modifications have also been made on the synthesized oligonucleotides, and previous reviews on the general synthesis of RNAs have not covered this area. In this tutorial review, three types of modifications have been summarized standing at the viewpoint of medicinal chemistry: (1) modifications on nucleobase, comprising substituent introduction and replacement with pseudobase; (2) modifications on ribose, consisting of modifications on the 2', 3' or 5'-position, alternation of configuration, and conformational restriction on ribose; (3) modifications on internucleoside linkages, including amide, formacetal, sulfide, sulfone, ether, phosphorothiolate and phosphorothioate linkages. Synthetic methods achieving these modifications along with the functions or values of these modifications have also been discussed and commented on.
authors.affiliation: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Haipin
authors.initials: H
authors.lastname: Zhou
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
mesh_terms: D002236:Carbohydrate Conformation; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D011685:Purine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry; D012313:RNA / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D012266:Ribose / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D011685:Purine Nucleotides; D011741:Pyrimidine Nucleosides; D012313:RNA; D012266:Ribose