onr:"swepub:oai:DiVA.org:liu-122842"
Sökning: onr:"swepub:oai:DiVA.org:liu-122842" > Novel Trans-Stilben...
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
- Campos Melo, Raúl IvanLinköpings universitet,Kemi,Tekniska fakulteten (författare)
Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
- 2016-05-19
- American Chemical Society (ACS),2016
- printrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:liu-122842
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122842URI
- https://doi.org/10.1021/acschemneuro.6b00062DOI
Kompletterande språkuppgifter
- Språk:engelska
- Sammanfattning på:engelska
Ingår i deldatabas
- SwePubSwePub
Klassifikation
Anmärkningar
- At the time for thesis presentation publication was in status: ManuscriptFunding agencies:The work was supported by Goran Gustafsson's Foundation (PH), The Swedish Research Council (PH), The Linkoping center for systemic neuroscience, LiU-Neuro, (XW), and Sven and Lilly Lawski's foundation (ME).
- Accumulation of misfolded transthyretin (TTR) as amyloid fibrils causes various human disorders. Native transthyretin is a neurotrophic protein and is a putative extracellular molecular chaperone. Several fluorophores have been shown in vitro to bind selectively to native TTR. Other compounds, such as thioflavin T, bind TTR amyloid fibrils. The probe 1-anilinonaphthalene-8-sulfonate (ANS) binds to both native and fibrillar TTR, becoming highly fluorescent, but with indistinguishable emission spectra for native and fibrillar TTR. Herein we report our efforts to develop a fluorescent small molecule capable of binding both native and misfolded protofibrillar TTR, providing distinguishable emission spectra. We used microwave synthesis for efficient production of a small library of trans-stilbenes and fluorescence spectral screening of their binding properties. We synthesized and tested 22 trans-stilbenes displaying a variety of functional groups. We successfully developed two naphthyl-based trans-stilbenes probes that detect both TTR states at physiological concentrations. The compounds bound with nanomolar to micromolar affinities and displayed distinct emission maxima upon binding native or misfolded protofibrillar TTR (>100 nm difference). The probes were mainly responsive to environment polarity providing evidence for the divergent hydrophobic structure of the binding sites of these protein conformational states. Furthermore, we were able to successfully use one of these probes to quantify the relative amounts of native and protofibrillar TTR in a dynamic equilibrium. In conclusion, we identified two trans-stilbene-based fluorescent probes, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (11) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (14), that bind native and protofibrillar TTR, providing a wide difference in emission maxima allowing conformational discrimination by fluorescence spectroscopy. We expect these novel molecules to serve as important chemical biology research tools in studies of TTR folding and misfolding.
Ämnesord och genrebeteckningar
- NATURVETENSKAP Kemi hsv//swe
- NATURAL SCIENCES Chemical Sciences hsv//eng
- transthyretin
- amyloid
- stilbene
- fluorescence
- probe
- spectrum
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Wu, XiongyuLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)xiowu62 (författare)
- Elgland, MathiasLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)matel79 (författare)
- Konradsson, PeterLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)petko14 (författare)
- Hammarström, PerLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)perha81 (författare)
- Linköpings universitetKemi (creator_code:org_t)
Sammanhörande titlar
- Ingår i:ACS Chemical Neuroscience: American Chemical Society (ACS)7:7, s. 924-9401948-7193
Internetlänk
Hitta via bibliotek
- ACS Chemical Neuroscience (Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
Hitta mer i SwePub
- Av författaren/redakt...
- Campos Melo, Raú ...
- Wu, Xiongyu
- Elgland, Mathias
- Konradsson, Pete ...
- Hammarström, Per
- Om ämnet
-
- NATURVETENSKAP
- NATURVETENSKAP
- och Kemi
- Artiklar i publikationen
- ACS Chemical Neu ...
- Av lärosätet
- Linköpings universitet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
