Studies on the synthesis of neamine-dinucleosides and neamine-PNA conjugates and their interaction with RNA.
Two types of neamine derivatives, neamine-dinucleotide conjugates 8a-g and neamine-PNA conjugates 12a-c and 14a-d, were synthesized. Compound 8a-g were synthesized by the condensation of azido-neamine with dinucleotide-5'-carboxylic acids, followed by reduction and deprotection. Compound 12a-c and 14a-d were synthesized by the similar strategy. The binding affinities of conjugates 8a-g, 12a-c, and 14a-d towards 16S RNA, 18S RNA, and TAR RNA were evaluated by SPR. It indicates that conjugates 12a-c and 14a-d interact with 16S, 18S RNA at the same level as that of neamine, 14a and 14d show about twofold binding affinities to TAR RNA compared to that of neamine. However, the neamine-dinucleotide conjugates 8a-g exhibit very weak binding affinities to 16S, 18S, and TAR RNA, computer modelling results that negative-negative electrostatic repulsion of phosphate group in compound 8a-g and RNA leads to a sharp decrease of the binding affinities compared with that of neamine, neamine-nucleoside and neamine-PNA conjugates.
Mei
Hui
H
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xueyuan Road #38, Beijing 100083, China.
Xing
Lei
L
Cai
Li
L
Jin
Hong-Wei
HW
Zhao
Peng
P
Yang
Zhen-Jun
ZJ
Zhang
Liang-Ren
LR
Zhang
Li-He
LH
D000225:Adenine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005601:Framycetin / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D009705:Nucleosides / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry; D012984:Software; D055672:Static Electricity; D020349:Surface Plasmon Resonance
D009705:Nucleosides; D020135:Peptide Nucleic Acids; D010710:Phosphates; D012336:RNA, Ribosomal, 16S; D005601:Framycetin; C488396:neamine; D012313:RNA; D000225:Adenine