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Molecular recognition of HIV-1 RNAs with branched peptides.

Authors
  • Peralta, Ashley N1
  • Dai, Yumin1
  • Sherpa, Chringma2
  • Le Grice, Stuart F J2
  • Santos, Webster L3
  • 1 Department of Chemistry and Center for Drug Discovery, Virginia Tech, Blacksburg, VA, United States. , (United States)
  • 2 Basic Research Laboratory, National Cancer Institute, Frederick, MD, United States. , (United States)
  • 3 Department of Chemistry and Center for Drug Discovery, Virginia Tech, Blacksburg, VA, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Methods in enzymology
Publication Date
Jan 01, 2019
Volume
623
Pages
373–400
Identifiers
DOI: 10.1016/bs.mie.2019.04.021
PMID: 31239054
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Targeting RNA offers the potential in many diseases of a therapeutic treatment. Due to its large surface area and ability to adopt different conformations, targeting RNA has proven challenging. Medium-sized branched peptides are of the size to competitively bind RNA while remaining cell permeable, stable in vivo, and non-toxic. Additionally, the ease in generating a large library followed by high-throughput screening provides a way to suggest a scaffold with high diversity that is capable of targeting the structure and sequence of RNA. The ability to select various types of amino acid modifications in the branched peptide allows for variable structures and interactions of the branched peptide but can result in too large a task if not approached properly. In this chapter, we discuss a strategy to selectively recognize RNAs of interest through high throughput screening of branched peptides, validation of hits and biophysical characterization, leading by example with our experience in targeting HIV-1 RNAs with branched peptides. © 2019 Elsevier Inc. All rights reserved.

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