RNA-Binding Macrocyclic Peptides

Being able to effectively target RNA with potent ligands will open up a large number of potential therapeutic options. The knowledge on how to achieve this is ever expanding but an important question that remains open is what chemical matter is suitable to achieve this goal. The high flexibility of...

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Main Authors: Sunit Pal, Peter ‘t Hart
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.883060/full
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author Sunit Pal
Peter ‘t Hart
author_facet Sunit Pal
Peter ‘t Hart
author_sort Sunit Pal
collection DOAJ
description Being able to effectively target RNA with potent ligands will open up a large number of potential therapeutic options. The knowledge on how to achieve this is ever expanding but an important question that remains open is what chemical matter is suitable to achieve this goal. The high flexibility of an RNA as well as its more limited chemical diversity and featureless binding sites can be difficult to target selectively but can be addressed by well-designed cyclic peptides. In this review we will provide an overview of reported cyclic peptide ligands for therapeutically relevant RNA targets and discuss the methods used to discover them. We will also provide critical insights into the properties required for potent and selective interaction and suggestions on how to assess these parameters. The use of cyclic peptides to target RNA is still in its infancy but the lessons learned from past examples can be adopted for the development of novel potent and selective ligands.
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spelling doaj.art-03b3ed734786460d9ac3528818a223352022-12-22T01:51:36ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-04-01910.3389/fmolb.2022.883060883060RNA-Binding Macrocyclic PeptidesSunit PalPeter ‘t HartBeing able to effectively target RNA with potent ligands will open up a large number of potential therapeutic options. The knowledge on how to achieve this is ever expanding but an important question that remains open is what chemical matter is suitable to achieve this goal. The high flexibility of an RNA as well as its more limited chemical diversity and featureless binding sites can be difficult to target selectively but can be addressed by well-designed cyclic peptides. In this review we will provide an overview of reported cyclic peptide ligands for therapeutically relevant RNA targets and discuss the methods used to discover them. We will also provide critical insights into the properties required for potent and selective interaction and suggestions on how to assess these parameters. The use of cyclic peptides to target RNA is still in its infancy but the lessons learned from past examples can be adopted for the development of novel potent and selective ligands.https://www.frontiersin.org/articles/10.3389/fmolb.2022.883060/fullmacrocyclic peptidesRNA bindingstructure-based designpeptide library screeningnatural products
spellingShingle Sunit Pal
Peter ‘t Hart
RNA-Binding Macrocyclic Peptides
Frontiers in Molecular Biosciences
macrocyclic peptides
RNA binding
structure-based design
peptide library screening
natural products
title RNA-Binding Macrocyclic Peptides
title_full RNA-Binding Macrocyclic Peptides
title_fullStr RNA-Binding Macrocyclic Peptides
title_full_unstemmed RNA-Binding Macrocyclic Peptides
title_short RNA-Binding Macrocyclic Peptides
title_sort rna binding macrocyclic peptides
topic macrocyclic peptides
RNA binding
structure-based design
peptide library screening
natural products
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.883060/full
work_keys_str_mv AT sunitpal rnabindingmacrocyclicpeptides
AT peterthart rnabindingmacrocyclicpeptides