Nucleoside derivative of 2' or 3' coupling amino acid, preparation method and application thereof

Abstract

The invention provides a nucleoside derivative of coupling amino acid, which has a structure shown as a formula 1 or a formula 2, wherein B is a nucleoside alkali radical with amino-protection radicals, n is an integer from 1 to 6, Linker is straight-chain paraffin from C2 to C10, R1 is H or a methyl, and R2 is a carbon-carbon ethylenic-bond, carbon-carbon acetylenic-bond or azide groups. The invention also provides the preparation method of the nucleoside derivative of the 2' or 3' coupling amino acid, and the application thereof to the improvement on the siRNA stability. SiRNA double strands immobilized by the nucleoside derivative of the 2' or 3' coupling amino acid provided by the invention has good lipotropy and membrane permeability, can tolerate the hydrolysis of various enzymes in organisms, and can tolerate wide pH environment and the reactions such as oxidization, reduction, replacement, elimination, addition and the like of the physiological environment. The chemical stability of the nucleoside derivative and the blood accommodating time are obviously improved.

Description

technical field The present invention relates to a 2' or 3' coupled amino acid nucleoside derivative, its preparation method and its application in the field of siRNA. Background technique The phenomenon of RNA interference (RNAi) is an evolutionarily conserved defense mechanism against the invasion of transgenic or foreign viruses. After the double-stranded RNA (double strand RNA, dsRNA) with a homologous and complementary sequence to the transcription product mRNA of the target gene is introduced into the cell, it can specifically degrade the mRNA, thereby resulting in the loss of the corresponding functional phenotype. This process belongs to transcription Posttranscriptional gene silencing (PTGS) category. RNAi widely exists in the biological world, from lower prokaryotes to plants, fungi, invertebrates, and even recently found in mammals, but the mechanism is more complicated. The mechanism of RNAi has been preliminarily elucidated: the first step of RNAi is dsRNA pr...

AI Technical Summary

Problems solved by technology

However, the existing modification and connection methods have very limited improvement on the stability of siRNA; moreover, it is not easy to introduce functional molecules into the modified structure, such as fluorescent labeling molecules

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