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De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries.

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Title: De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries.
Authors: Yang L; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA., Behera A; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA., Meyers HJ; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA., Wang T; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Source: Chembiochem : a European journal of chemical biology [Chembiochem] 2026 Sep 28; Vol. 27 (18), pp. e70532.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Wiley-VCH Verlag Country of Publication: Germany NLM ID: 100937360 Publication Model: Print Cited Medium: Internet ISSN: 1439-7633 (Electronic) Linking ISSN: 14394227 NLM ISO Abbreviation: Chembiochem Subsets: MEDLINE
Imprint Name(s): Original Publication: Weinheim, Germany : Wiley-VCH Verlag, c2000-
MeSH Terms: Peptides, Cyclic*/genetics , Peptides, Cyclic*/chemistry , Peptides, Cyclic*/pharmacology , Peptides, Cyclic*/metabolism , Drug Discovery*/methods , Peptide Library*, Humans ; Animals
Abstract: Cellular selection has emerged as a powerful approach for high throughput de novo discovery of bioactive cyclic peptides (CPs). This strategy coexpresses genetically encoded CP libraries with the target of interest in cells and uses customizable selection systems to link desired CP activities to a selectable phenotype to directly identify functional inhibitors. Cellular selections have yielded many CP inhibitors against a diverse range of therapeutic targets and have been continuously empowered by expansions in the CP diversity and selection repertoire. In this review, we summarize studies on cellular selection using genetically encoded CP libraries and discuss opportunities for future application of this technology.
(© 2026 The Author(s). ChemBioChem published by Wiley‐VCH GmbH.)
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Grant Information: R35 GM159851 United States GM NIGMS NIH HHS; R35 GM159851 United States NH NIH HHS
Contributed Indexing: Keywords: cyclic peptide; genetic selections; peptides
Substance Nomenclature: 0 (Peptides, Cyclic)
0 (Peptide Library)
Entry Date(s): Date Created: 20260923 Date Completed: 20260923 Latest Revision: 20260925
Update Code: 20260925
PubMed Central ID: PMC13599706
DOI: 10.1002/cbic.70532
PMID: 42775926
Database: MEDLINE
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  Data: De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries.
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  Data: <searchLink fieldCode="AU" term="%22Yang+L%22">Yang L</searchLink>; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.<br /><searchLink fieldCode="AU" term="%22Behera+A%22">Behera A</searchLink>; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.<br /><searchLink fieldCode="AU" term="%22Meyers+HJ%22">Meyers HJ</searchLink>; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.<br /><searchLink fieldCode="AU" term="%22Wang+T%22">Wang T</searchLink>; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
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  Data: <searchLink fieldCode="JN" term="%22100937360%22">Chembiochem : a European journal of chemical biology</searchLink> [Chembiochem] 2026 Sep 28; Vol. 27 (18), pp. e70532.
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  Data: Journal Article; Review
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Wiley-VCH+Verlag%22">Wiley-VCH Verlag </searchLink><i>Country of Publication: </i>Germany <i>NLM ID: </i>100937360 <i>Publication Model: </i>Print <i>Cited Medium: </i>Internet <i>ISSN: </i>1439-7633 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2214394227%22">14394227 </searchLink><i>NLM ISO Abbreviation: </i>Chembiochem <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Weinheim, Germany : Wiley-VCH Verlag, c2000-
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  Data: <searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic%22">Peptides, Cyclic*</searchLink>/<searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic%22">Peptides, Cyclic*</searchLink>/<searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic%22">Peptides, Cyclic*</searchLink>/<searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic%22">Peptides, Cyclic*</searchLink>/<searchLink fieldCode="MM" term="%22Peptides%2C+Cyclic+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Drug+Discovery%22">Drug Discovery*</searchLink>/<searchLink fieldCode="MM" term="%22Drug+Discovery+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Peptide+Library%22">Peptide Library*</searchLink><br /><searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Cellular selection has emerged as a powerful approach for high throughput de novo discovery of bioactive cyclic peptides (CPs). This strategy coexpresses genetically encoded CP libraries with the target of interest in cells and uses customizable selection systems to link desired CP activities to a selectable phenotype to directly identify functional inhibitors. Cellular selections have yielded many CP inhibitors against a diverse range of therapeutic targets and have been continuously empowered by expansions in the CP diversity and selection repertoire. In this review, we summarize studies on cellular selection using genetically encoded CP libraries and discuss opportunities for future application of this technology.<br /> (© 2026 The Author(s). ChemBioChem published by Wiley‐VCH GmbH.)
– Name: Ref
  Label: References
  Group: RefInfo
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  Data: R35 GM159851 United States GM NIGMS NIH HHS; R35 GM159851 United States NH NIH HHS
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>cyclic peptide; genetic selections; peptides
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  Label: Substance Nomenclature
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  Data: 0 (Peptides, Cyclic)<br />0 (Peptide Library)
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  Data: <i>Date Created: </i>20260923 <i>Date Completed: </i>20260923 <i>Latest Revision: </i>20260925
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  Data: 10.1002/cbic.70532
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  Label: PMID
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  Data: 42775926
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42775926
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      – Type: doi
        Value: 10.1002/cbic.70532
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: e70532
    Subjects:
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Peptides, Cyclic genetics
        Type: general
      – SubjectFull: Peptides, Cyclic chemistry
        Type: general
      – SubjectFull: Peptides, Cyclic pharmacology
        Type: general
      – SubjectFull: Peptides, Cyclic metabolism
        Type: general
      – SubjectFull: Drug Discovery methods
        Type: general
      – SubjectFull: Peptide Library
        Type: general
    Titles:
      – TitleFull: De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries.
        Type: main
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            – D: 28
              M: 09
              Text: 2026 Sep 28
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1439-7633
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              Value: 27
            – Type: issue
              Value: 18
          Titles:
            – TitleFull: Chembiochem : a European journal of chemical biology
              Type: main
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