Covalent stabilization of a small molecule-RNA complex

Hayden Peacock, Radhika Bachu, Peter A. Beal

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)5002-5005
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number17
DOIs
StatePublished - Sep 1 2011

Fingerprint

Stabilization
RNA
Peptides
Molecules
Nucleotide Aptamers
Cysteamine
Covalent bonds
Binding Sites
DNA
N-bromoacetamide

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

Cite this

Covalent stabilization of a small molecule-RNA complex. / Peacock, Hayden; Bachu, Radhika; Beal, Peter A.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 17, 01.09.2011, p. 5002-5005.

Research output: Contribution to journalArticle

Peacock, Hayden ; Bachu, Radhika ; Beal, Peter A. / Covalent stabilization of a small molecule-RNA complex. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 17. pp. 5002-5005.
@article{06c29587eba745d69923d2ca730ddbc4,
title = "Covalent stabilization of a small molecule-RNA complex",
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.",
keywords = "Aptamer, Covalent tethering, Helix-threading peptide, Nucleoside analog, Templated reaction",
author = "Hayden Peacock and Radhika Bachu and Beal, {Peter A.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1016/j.bmcl.2011.04.136",
language = "English (US)",
volume = "21",
pages = "5002--5005",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "17",

}

TY - JOUR

T1 - Covalent stabilization of a small molecule-RNA complex

AU - Peacock, Hayden

AU - Bachu, Radhika

AU - Beal, Peter A.

PY - 2011/9/1

Y1 - 2011/9/1

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

UR - http://www.scopus.com/inward/record.url?scp=80051795315&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051795315&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2011.04.136

DO - 10.1016/j.bmcl.2011.04.136

M3 - Article

VL - 21

SP - 5002

EP - 5005

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 17

ER -