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dc.contributor.authorCheng , Chunwei
Liu, Yan
Balasis, Maria E.
Garner, Thomas P.
Li, Jerry
Simmons, Nicholas L.
Berndt, Norbert
Song, Hao
Pan, Lili
Qin, Yong
Nicolaou, K.C.
Gavathiotis, Evripidis
Sebti , Said M.
Li, Rongshi
dc.date.accessioned 2014-08-29T20:22:43Z
dc.date.available 2014-08-29T20:22:43Z
dc.date.issued 2014
dc.identifier.citation Cheng , Chunwei, Liu, Yan, Balasis, Maria E., et al.. "Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim." Marine Drugs, 12, (2014) MDPI: 4311-4325. http://dx.doi.org/10.3390/md12084311.
dc.identifier.urihttps://hdl.handle.net/1911/77133
dc.description.abstract A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation.
dc.language.iso eng
dc.publisher MDPI
dc.rights This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.title Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim
dc.type Journal article
dc.contributor.funder Skaggs Institute for Chemical Biology
dc.contributor.funder National Institutes of Health
dc.citation.journalTitle Marine Drugs
dc.contributor.org BioScience Research Collaborative
dc.subject.keywordmarinopyrroles
protein-protein interaction disruptors
apoptosis
SAR
dc.citation.volumeNumber 12
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.3390/md12084311
dc.identifier.pmcid PMC4145318
dc.identifier.pmid 25076060
dc.identifier.grantID R00 HL095929 (National Institutes of Health)
dc.identifier.grantID P30CA013330-39S1 (National Institutes of Health)
dc.type.publication publisher version
dc.citation.firstpage 4311
dc.citation.lastpage 4325


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