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dc.contributor.author배애님-
dc.contributor.author임상민-
dc.contributor.author앰빌리-
dc.contributor.author김태훈-
dc.contributor.author정서윤-
dc.date.accessioned2021-06-09T04:18:53Z-
dc.date.available2021-06-09T04:18:53Z-
dc.date.issued2017-12-
dc.identifier.citationVOL 90, NO 6-1055-
dc.identifier.issn1747-0277-
dc.identifier.other49698-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/66562-
dc.description.abstractPresent work aimed to introduce non-peptidic ABAD loop D (LD) hot spot mimetics as ABAD-Aβ inhibitors. A full-length atomistic model of ABAD-Aβ complex was built as a scaffold to launch the lead design and its topology later verified by cross-checking the computational mutagenesis results with that of in vitro data. Thereafter, the interactions of prime Aβ-binding LD residues&#8212-
dc.description.abstractTyr101, Thr108, and Thr110&#8212-
dc.description.abstractwere translated into specific pharmacophore features and this hypothesis subsequently used as a virtual screen query. ELISA-based screening of 20 hits identified two promising lead candidates, VC15 and VC19 with an IC50 of 4.4 ± 0.3 and 9.6 ± 0.1 μm, respectively. They productively reversed Aβ-induced mitochondrial dysfunctions such as mitochondrial membrane potential loss (JC-1 assay), toxicity (MTT assay), and ATP reduction (ATP assay) in addition to increased cell viabilities. This is the first reporting of LD hot spot-centric in silico scheme to discover novel compounds with promising ABAD-Aβ inhibitory potential. These chemotypes are proposed for further structural optimization to derive novel Alzheimer's disease (AD) therapeutics.-
dc.publisherChemical biology & drug design-
dc.subjectAlzeheimer's disease-
dc.subjectABAD-
dc.subjectvirtual screening-
dc.titleIn silico-designed novel non-peptidic ABAD L-D hot spot mimetics reverse A-induced mitochondrial impairments in vitro-
dc.typeArticle-
dc.relation.page10411055-
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