A Generalizable DNA‐Catalyzed Approach to Peptide–Nucleic Acid Conjugation. Issue 13 (23rd July 2014)

• Record Type: Journal Article
• Authors: Chu, Chih‐Chi; Wong, On Yi; Silverman, Scott K.
• Is Part Of: Chembiochem. Volume 15:Issue 13(2014)
• Page Start: 1905
• Page End: 1910
• Publication Date: 2014-07-23
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402255
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>We report DNA catalysts (deoxyribozymes) that join tyrosine‐containing peptides to RNA and DNA in one step and without requiring protecting groups on either the peptide or the nucleic acid. Our previous efforts towards this goal required tethering the peptide to a DNA anchor oligonucleotide. Here, we established direct in vitro selection for deoxyribozymes that use untethered, free peptide substrates. This approach enables imposition of selection pressure via reduced peptide concentration and leads to preparatively useful lower apparent <italic>K</italic>_m values of ∼100 μ<sc>M</sc> peptide. Use of phosphorimidazolide (Imp) rather than triphosphate as the electrophile enables reactivity of either terminus (5′ or 3′) of both RNA and DNA. Our findings establish a generalizable means of joining unprotected peptide to nucleic acid in one step by using DNA catalysts identified by in vitro selection.</p> </abstract>