Covalent stabilization of a small molecule-RNA complex

Hayden Peacock; Radhika Bachu; Peter A. Beal

doi:10.1016/j.bmcl.2011.04.136

Covalent stabilization of a small molecule-RNA complex

Hayden Peacock, Radhika Bachu, Peter A. Beal

Chemistry

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

We demonstrate covalent bond formation between an RNA aptamer containing a cysteamine-tethered nucleobase and helix-threading peptides (HTPs) containing α-bromoacetamide N-termini. The reaction is high yielding and inhibited by a DNA strand Watson-Crick complementary to the aptamer sequence indicating covalent reaction is dependent on the high affinity HTP-binding site present in the folded aptamer. These results are important for future structural studies of HTP-RNA complexes and methods for the discovery of new high affinity analogs via covalent tethering strategies.

Original language	English (US)
Pages (from-to)	5002-5005
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2011.04.136
State	Published - Sep 1 2011

Keywords

Aptamer
Covalent tethering
Helix-threading peptide
Nucleoside analog
Templated reaction

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

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abstract = "We demonstrate covalent bond formation between an RNA aptamer containing a cysteamine-tethered nucleobase and helix-threading peptides (HTPs) containing α-bromoacetamide N-termini. The reaction is high yielding and inhibited by a DNA strand Watson-Crick complementary to the aptamer sequence indicating covalent reaction is dependent on the high affinity HTP-binding site present in the folded aptamer. These results are important for future structural studies of HTP-RNA complexes and methods for the discovery of new high affinity analogs via covalent tethering strategies.",

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AU - Peacock, Hayden

AU - Bachu, Radhika

AU - Beal, Peter A.

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N2 - We demonstrate covalent bond formation between an RNA aptamer containing a cysteamine-tethered nucleobase and helix-threading peptides (HTPs) containing α-bromoacetamide N-termini. The reaction is high yielding and inhibited by a DNA strand Watson-Crick complementary to the aptamer sequence indicating covalent reaction is dependent on the high affinity HTP-binding site present in the folded aptamer. These results are important for future structural studies of HTP-RNA complexes and methods for the discovery of new high affinity analogs via covalent tethering strategies.

AB - We demonstrate covalent bond formation between an RNA aptamer containing a cysteamine-tethered nucleobase and helix-threading peptides (HTPs) containing α-bromoacetamide N-termini. The reaction is high yielding and inhibited by a DNA strand Watson-Crick complementary to the aptamer sequence indicating covalent reaction is dependent on the high affinity HTP-binding site present in the folded aptamer. These results are important for future structural studies of HTP-RNA complexes and methods for the discovery of new high affinity analogs via covalent tethering strategies.

KW - Aptamer

KW - Covalent tethering

KW - Helix-threading peptide

KW - Nucleoside analog

KW - Templated reaction

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Covalent stabilization of a small molecule-RNA complex

Abstract

Keywords

ASJC Scopus subject areas

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