LABELED NUCLEOTIDE ANALOGS HAVING PROTEIN SHIELDS

摘要

Compositions, methods, and systems are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The nucleotide analogs have two avidin proteins connected by a central dye component, and each avidin protein is further connected to a nucleotide component. The protein can prevent the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.

主权项

1. A labeled nucleotide analog comprising:
two avidin proteins connected through a central dye component, the central dye component comprising one or more dye moieties, the central dye component further comprising two bis-biotin moieties, each of the bis-biotin moieties bound to one of the avidin proteins,
wherein one of the avidin proteins is also bound to a first nucleotide component through a bis-biotin moiety, wherein the first nucleotide component comprises one or more phospholinked nucleotides, andwherein the other avidin protein is also bound to a first nucleotide component through a bis-biotin moiety, wherein the first nucleotide component comprises one or more phospholinked nucleotides.