Source 1review2015ChemMedChem
Toolkit/cyclic peptides
cyclic peptides
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
One way to improve these properties is to constrain the secondary structure of linear peptides by cyclisation. Herein we review various classes of cyclic and macrocyclic peptides as chemical probes of protein surfaces and modulators of PPIs.
Usefulness & Problems
Why this is useful
Cyclic peptides are presented as chemical probes and modulators that can recognize protein surfaces and interfere with protein–protein interactions. The review frames cyclisation as a way to constrain peptide structure for this purpose.; recognizing protein surfaces; probing protein–protein interactions; modulating protein–protein interactions
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Cyclic peptides are presented as chemical probes and modulators that can recognize protein surfaces and interfere with protein–protein interactions. The review frames cyclisation as a way to constrain peptide structure for this purpose.
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recognizing protein surfaces
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probing protein–protein interactions
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modulating protein–protein interactions
Problem solved
They address the difficulty of targeting shallow protein surfaces and PPIs that are hard to engage with small molecules. They also aim to improve the biological usability of linear peptides.; providing peptide-like binders for shallow protein surfaces that are difficult for small molecules to target; improving some liabilities of linear peptides through cyclisation
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They address the difficulty of targeting shallow protein surfaces and PPIs that are hard to engage with small molecules. They also aim to improve the biological usability of linear peptides.
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providing peptide-like binders for shallow protein surfaces that are difficult for small molecules to target
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improving some liabilities of linear peptides through cyclisation
Problem links
improving some liabilities of linear peptides through cyclisation
LiteratureThey address the difficulty of targeting shallow protein surfaces and PPIs that are hard to engage with small molecules. They also aim to improve the biological usability of linear peptides.
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They address the difficulty of targeting shallow protein surfaces and PPIs that are hard to engage with small molecules. They also aim to improve the biological usability of linear peptides.
providing peptide-like binders for shallow protein surfaces that are difficult for small molecules to target
LiteratureThey address the difficulty of targeting shallow protein surfaces and PPIs that are hard to engage with small molecules. They also aim to improve the biological usability of linear peptides.
Source:
They address the difficulty of targeting shallow protein surfaces and PPIs that are hard to engage with small molecules. They also aim to improve the biological usability of linear peptides.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
conformational constraint by cyclisationprotein–protein interaction modulationprotein-surface recognitionTechniques
Structural CharacterizationTarget processes
No target processes tagged yet.
Input: Chemical
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: actuator
Implementation requires peptide design and a cyclisation strategy that constrains the secondary structure of a linear peptide. The abstract does not specify a particular chemistry or screening platform.; requires constraining linear peptides by cyclisation to improve properties for biological application
The abstract indicates that peptides as a class suffer from low intracellular stability, poor permeability, and high in vivo clearance. It does not claim that cyclisation fully eliminates these liabilities.; peptides have inherently low intracellular stability; peptides have limited permeability; peptides have high in vivo clearance
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Cyclisation can improve peptide properties by constraining the secondary structure of linear peptides.
Recent advances support the potential of peptide-like molecules to specifically target protein–protein interactions.
Peptides have limited biological application because of low intracellular stability, low permeability, and high in vivo clearance.
Peptides are suitable candidates for targeting protein surfaces because they can closely mimic structural features of protein interfaces.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug cyclic-peptides
One way to improve these properties is to constrain the secondary structure of linear peptides by cyclisation. Herein we review various classes of cyclic and macrocyclic peptides as chemical probes of protein surfaces and modulators of PPIs.
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engineering strategysupports
Cyclisation can improve peptide properties by constraining the secondary structure of linear peptides.
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limitation statementsupports
Peptides have limited biological application because of low intracellular stability, low permeability, and high in vivo clearance.
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modality rationalesupports
Peptides are suitable candidates for targeting protein surfaces because they can closely mimic structural features of protein interfaces.
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Comparisons
Source-stated alternatives
Small molecules are explicitly contrasted as a modality that struggles with shallow protein surfaces and lack of deep binding pockets. The abstract does not name other peptide-engineering alternatives.
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Small molecules are explicitly contrasted as a modality that struggles with shallow protein surfaces and lack of deep binding pockets. The abstract does not name other peptide-engineering alternatives.
Source-backed strengths
can closely mimic many structural features of protein interfaces; cyclisation is presented as a way to improve peptide properties
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can closely mimic many structural features of protein interfaces
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cyclisation is presented as a way to improve peptide properties
Compared with bacterial degrons
cyclic peptides and bacterial degrons address a similar problem space.
Shared frame: same top-level item type; same primary input modality: chemical
cyclic peptides and Pyr-NHS-functionalised 3D graphene foam electrode biosensor address a similar problem space.
Shared frame: same top-level item type; same primary input modality: chemical
Compared with rM3Ds
cyclic peptides and rM3Ds address a similar problem space.
Shared frame: same top-level item type; same primary input modality: chemical
Ranked Citations
- 1.