Methods of ligating expressed proteins

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for...

Reexamination Certificate

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C435S069100, C435S069700, C435S173300, C530S334000, C530S350000

Reexamination Certificate

active

06875594

ABSTRACT:
The present invention provides a method of cleaving a recombinantly expressed protein from an intein and ligating the protein to a peptide containing an N-terminal cysteine having an unoxidized sulfhydryl side chain which comprises contacting the protein with the peptide in a reaction solution comprising a conjugated thiophenol, thereby forming a C-terminal thioester of the recombinant protein which spontaneously rearranges intramolecularly to form an amide bond linking the protein to the peptide. The present invention also provides a method of producing a protein-chip composition comprising the steps of: (a) contacting a solid support chip containing an amine group with a peptide containing an N-terminal cysteine having an unoxidized sulfhydryl side chain thereby covalently linking the peptide to the solid support, forming a peptide-chip; and (b) contacting a recombinant protein having an intein domain with the peptide-chip of step (a) with a reaction solution containing a conjugated thiophenol, thereby forming a C-terminal thioester of the recombinant protein which spontaneously rearranges intramoleculaly to form an amide bond covalently linking the protein to the peptide-chip, thereby producing a protein-chip composition.

REFERENCES:
patent: 5834247 (1998-11-01), Comb et al.
patent: 9634878 (1996-11-01), None
Dawson et al., Science vol. 266 (Nov. 1994) pp. 776-779.*
Dawson et al., JACS vol. 119, No. 19 (May 1997) pp. 4325-4329.*
Chong et al., Gene (Jun. 1997) pp. 271-281.*
Severinov et al., J. Biol. Chem. vol. 273, No. 26 (Jun. 26, 1998) pp. 16205-16209.

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