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In silico studies o...
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Zhou, YangUppsala universitet,Kemisk och biomolekylär fysik,Jinan Univ, Sch Pharm, Guangzhou 510632, Peoples R China.
(författare)
In silico studies of ASEM analogues targeting alpha 7-nAChR and experimental verification
- Artikel/kapitelEngelska2021
Förlag, utgivningsår, omfång ...
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2021
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ROYAL SOC CHEMISTRY,2021
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-291942
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-291942URI
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https://doi.org/10.1039/d0ra10435cDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:145876922URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-437881URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20210324
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The alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) is implicated in a variety of neurodegenerative and neuropsychiatric disorders, such as Alzheimer's disease (AD) and schizophrenia. The progress of these disorders can be studied using positron emission tomography (PET) with radiotracers for alpha 7-nAChR. [F-18]ASEM and [F-18] para-ASEM (also referred to as [F-18]DBT-10) are novel and potent alpha 7-nAChR PET radiotracers which have successfully been used in human subjects and nonhuman primates, though further improvement of them is still a pressing task in the community of neurodegeneration research. In this work, we demonstrate the use of modern in silico techniques to predict the binding modes, binding strengths, and residence times for molecular PET tracers binding to proteins, using ASEM and DBT-10 as a showcase of the predictive and interpretational power of such techniques, in particular free energy perturbation theory. The corresponding compounds were synthesized and further tested by in vitro binding experiment for validation. Encouragingly, our in silico modeling can correctly predict the binding affinities of the ASEM analogues. The structure-activity relationships for the ortho- and para-substitutions are well explained at the atomistic level and provide structure-based guiding for the future development of PET tracers for alpha 7-nAChR. A discussion is presented on the complementary use of in silico rational methods based on atomic and electronic principles for in vitro characterization of PET tracers.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Guanglin, Kuang,1987-KTH,Teoretisk kemi och biologi,AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.(Swepub:kth)u1lyo20l
(författare)
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Li, JunhaoKTH,Teoretisk kemi och biologi,AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.(Swepub:kth)u1wxbd82
(författare)
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Halldin, ChristerKarolinska Institutet,Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, S-17176 Stockholm, Sweden.
(författare)
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Nordberg, AgnetaKarolinska Institutet,Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Nordberg Translat Mol Imaging Lab,Div Clin Geriat, S-14184 Stockholm, Sweden.;Theme Aging Karolinska Univ Hosp, S-14186 Stockholm, Sweden.
(författare)
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Långström, BengtUppsala universitet,Organisk kemi(Swepub:uu)benglang
(författare)
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Tu, YaoquanKTH,Teoretisk kemi och biologi,AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.(Swepub:kth)u1kuh2ie
(författare)
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Ågren, HansUppsala universitet,Kemisk och biomolekylär fysik,Henan Univ, Coll Chem & Chem Engn, Kaifeng 475004, Henan, Peoples R China.(Swepub:uu)hanag788
(författare)
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Uppsala universitetKemisk och biomolekylär fysik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:RSC Advances: ROYAL SOC CHEMISTRY11:7, s. 3942-39512046-2069
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