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

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 (3,40-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.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87680
Date26 October 2023
CreatorsPaschold, André, Voigt, Bruno, Hause, Gerd, Kohlmann, Tim, Rothemund, Sven, Binder, Wolfgang H.
PublisherMDPI
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation1512

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