Short peptide pharmacophores developed from protein phosphatase-1 disrupting peptides (PDPs)
Abstract: PP1 is a major phosphoserine/threonine-specific phosphatase that is involved in diseases such as heart insufficiency and diabetes. PP1-disrupting peptides (PDPs) are selective modulators of PP1 activity that release its catalytic subunit, which then dephosphorylates nearby substrates. Recently, PDPs enabled the creation of phosphatase-recruiting chimeras, which are bifunctional molecules that guide PP1 to a kinase to dephosphorylate and inactivate it. However, PDPs are 23mer peptides, which is not optimal for their use in therapy due to potential stability and immunogenicity issues. Therefore, we present here the sequence optimization of the 23mer PDP to a 5mer peptide, involving several attempts considering structure-based virtual screening, high throughput screening and peptide sequence optimization. We provide here a strong pharmacophore as lead structure to enable PP1 targeting in therapy or its use in phosphatase-recruiting chimeras in the future
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Bioorganic & medicinal chemistry. - 65 (2022) , 116785, ISSN: 1464-3391
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2022
- Creator
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Fontanillo, Miriam
Trębacz, Małgorzata
Reinkemeier, Christopher Dieter
Avilés Huerta, Daniela
Uhrig, Ulrike C.
Sehr, Peter
Köhn, Maja
- Contributor
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Abteilung Integrative Signalforschung
- DOI
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10.1016/j.bmc.2022.116785
- URN
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urn:nbn:de:bsz:25-freidok-2294958
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:54 PM CET
Data provider
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Fontanillo, Miriam
- Trębacz, Małgorzata
- Reinkemeier, Christopher Dieter
- Avilés Huerta, Daniela
- Uhrig, Ulrike C.
- Sehr, Peter
- Köhn, Maja
- Abteilung Integrative Signalforschung
- Universität
Time of origin
- 2022
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Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides
Nonribosomal peptide synthetases : quaternary structure and chemoenzymatic synthesis of macrocyclic peptides
Peptides in Plasma, Urine, and Dialysate : Toward Unravelling Renal Peptide Handling
Development of new antimicrobial peptides based on the synthetic peptide NK-2
Prediction and verification of novel peptide targets of protein tyrosine phosphatase 1B
Expression of short peptides in vivo to modulate protein interactions
Thioacid-Containing Peptides for the Convergent Synthesis of N-Glycopeptides and Peptide Conjugates
Peptide antibiotics - biosynthesis and functions : enzymatic formation of bioactive peptides and related compounds
Phosphoprotein phosphatase substrates - selectivity from peptides to proteins
Coarse-grained peptide models: conformational sampling, peptide association and dynamical properties for peptides
Development of a photoactivatable protein phosphatase-1-disrupting peptide
Cationic antimicrobial peptides : thermodynamic characterization of peptide-lipid interactions and biological efficacy of surface-tethered peptides
Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides
Nonribosomal peptide synthetases : quaternary structure and chemoenzymatic synthesis of macrocyclic peptides
Peptides in Plasma, Urine, and Dialysate : Toward Unravelling Renal Peptide Handling
Development of new antimicrobial peptides based on the synthetic peptide NK-2
Prediction and verification of novel peptide targets of protein tyrosine phosphatase 1B
Expression of short peptides in vivo to modulate protein interactions
Thioacid-Containing Peptides for the Convergent Synthesis of N-Glycopeptides and Peptide Conjugates