β-Turn mimetic synthetic peptides as amyloid-β aggregation inhibitors

Deike, Stefanie; Rothemund, Sven; Voigt, Bruno; Samantray, Suman; Strodel, Birgit; Binder, Wolfgang H.

doi:10.1016/j.bioorg.2020.104012

Cited by 20 publications

(30 citation statements)

References 49 publications

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“…In further experiments, we investigated the (catalytic) influence of the AzoPTH 25–37 isomers on the fibrillization of PTH 25–37 ( Figure 6 ). We previously observed such catalytic effects of β-turn modified amyloids (Aβ) on the fibrillization of the Alzheimer peptide Aβ 1–40 [ 49 ]. Thus 100 μM of PTH 25–37 were fibrillized in the presence of various concentrations of the respective AzoPTH 25–37 isomer (10/20/50/100 μM).…”

Section: Resultsmentioning

confidence: 99%

Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities

et al. 2022

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We here report a novel strategy to control the bioavailability of the fibrillizing parathyroid hormone (PTH)-derived peptides, where the concentration of the bioactive form is controlled by an reversible, photoswitchable peptide. PTH1–84, a human hormone secreted by the parathyroid glands, is important for the maintenance of extracellular fluid calcium and phosphorus homeostasis. Controlling fibrillization of PTH1–84 represents an important approach for in vivo applications, in view of the pharmaceutical applications for this protein. We embed the azobenzene derivate 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (3,4′-AMPB) into the PTH-derived peptide PTH25–37 to generate the artificial peptide AzoPTH25–37 via solid-phase synthesis. AzoPTH25–37 shows excellent photostability (more than 20 h in the dark) and can be reversibly photoswitched between its cis/trans forms. As investigated by ThT-monitored fibrillization assays, the trans-form of AzoPTH25–37 fibrillizes similar to PTH25–37, while the cis-form of AzoPTH25–37 generates only amorphous aggregates. Additionally, cis-AzoPTH25–37 catalytically inhibits the fibrillization of PTH25–37 in ratios of up to one-fifth. The approach reported here is designed to control the concentration of PTH-peptides, where the bioactive form can be catalytically controlled by an added photoswitchable peptide.

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Section: Resultsmentioning

confidence: 99%

Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities

et al. 2022

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“…13,16 A particularly promising direction is the use of oxetane modification to stabilise or mimic -turn structures. -turn structural motifs are widespread in proteins, have been implicated in molecular recognition and proteinprotein interactions for proteins including GPCRs 44 and amyloid-, 45 and are of considerable interest in the field of peptidomimetics for therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

Impact of oxetane incorporation on the structure and stability of alpha-helical peptides

Jayawant

Beadle

Wilkening

et al. 2020

Phys. Chem. Chem. Phys.

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“…The fibrillation of amyloid proteins and peptides Aβ [ 40 ] is responsible for several neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. Inhibitors that prevent amyloid aggregation have recently been studied [ 41 ], including the synthesis of β-turn mime conjugates by replacing two amino acids in the turn region of peptide Aβ by the triazole moiety. The synthesis of the triazole aromatic β-turn mime was carried out under the conditions of CuAAC between Fmoc-protected 3-ethynyl aniline and 3-azidobenzoic acid.…”

Section: 123- Triazole Moiety and Peptide Structurementioning

confidence: 99%

1,2,3-Triazoles as Biomimetics in Peptide Science

2021

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Natural peptides are an important class of chemical mediators, essential for most vital processes. What limits the potential of the use of peptides as drugs is their low bioavailability and enzymatic degradation in vivo. To overcome this limitation, the development of new molecules mimicking peptides is of great importance for the development of new biologically active molecules. Therefore, replacing the amide bond in a peptide with a heterocyclic bioisostere, such as the 1,2,3-triazole ring, can be considered an effective solution for the synthesis of biologically relevant peptidomimetics. These 1,2,3-triazoles may have an interesting biological activity, because they behave as rigid link units, which can mimic the electronic properties of amide bonds and show bioisosteric effects. Additionally, triazole can be used as a linker moiety to link peptides to other functional groups.

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β-Turn mimetic synthetic peptides as amyloid-β aggregation inhibitors

Cited by 20 publications

References 49 publications

Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities

Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities

Impact of oxetane incorporation on the structure and stability of alpha-helical peptides

1,2,3-Triazoles as Biomimetics in Peptide Science

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