Compositions and methods for conjugating oligonucleotides

摘要

An oligonucleotide derivative having the structure of formula (A) and methods for preparing the oligonucleotide derivative are disclosed. wherein R3 is a first oligonucleotide; R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, a polyethylene glycol, a peptide, a protein, a polysaccharide, and a second oligonucleotide; R2 is a linker or a direct bond; Z1 is NR4, S, or O, and Z2 is NR4 or S, wherein R4 is selected from H, alkyl, aryl, heterocyclyl, or heteroaryl. A method includes: synthesizing an oligonucleotide derivative comprising an amino or thiol group; and reacting a 3,4-dialkoxycyclobutene-1,2-dione with the oligonucleotide derivative to produce an oligonucleotide-squarate mono-conjugate.

主权项

1. An oligonucleotide derivative having the structure of formula (A):wherein R3 is a first oligonucleotide; R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R2 is a selected from a (C1-C12) hydrocarbyl chain and a polyethylene glycol linker attached to a 5′ hydroxy group, a 3′ hydroxy group, or an exocyclic amino group on a nucleobase of the first oligonucleotide, wherein (C1-C12) hydrocarbyl chain is optionally substituted with a group selected from —O—R″, —O—CO—R″, —NR′—R″, —NR′—CO—R″, —CO—NR′—R″, —CO—R″, —CN, halogen, or a combination thereof, wherein R′ and R″ are independently H or (C1-C6) hydrocarbyl; Z1 is S, or O, and Z2 is NR4 or S, wherein R4 is selected from H, alkyl, aryl, heterocyclyl, or heteroaryl.