title: Design, synthesis and properties of artificial nucleic acids from (R)-4-amino-butane-1,3-diol.
abstract: A new artificial nucleic acid analogue, (R)-Am-BuNA, was developed with a simplified acyclic (R)-4-amino-butane-1,3-diol phosphodiester backbone. Phosphoramidite monomers of (R)-Am-BuNA were incorporated into DNA oligonucleotides (ODNs) and G-quadruplexes. Their thermal stability, conformation change and biological stability were further investigated using UV-melting, circular dichroism (CD) and gel electrophoresis. The results suggested that thermal stability of the duplexes of (R)-Am-BuNA modified ODNs and their complementary ODN is highly dependent on the substitution position. Substitution of thymidine at the 7th position in a thrombin-binding DNA aptamer (TBA) results in a slight increase in Tm with no effect on quadruplex conformation on the CD spectrum in comparison to that of the natural G-quadruplex. Further enzymatic experiments with fetal bovine serum (FBS) and snake venom phosphodiesterase (SVPDE) indicated that only single replacement of a (R)-Am-BuNA modified nucleobase greatly inhibited oligonucleotide degradation, which shows their promising applications as capping nucleotides in nucleic acid drugs.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China, and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. xinjingt@bjmu.edu.cn.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.forename: Meng
authors.initials: M
authors.lastname: Su
authors.forename: Xiaogai
authors.initials: X
authors.lastname: Yang
authors.forename: Xinjing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000440:Butanols / Q000737:chemistry*; D002082:Butylamines / Q000737:chemistry*; D015195:Drug Design; D015394:Molecular Structure; D009696:Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000440:Butanols; D002082:Butylamines; D009696:Nucleic Acids