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SAR by kinetics for...
SAR by kinetics for drug discovery in protein misfolding diseases
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- Chia, Sean (författare)
- University of Cambridge
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- Habchi, Johnny (författare)
- University of Cambridge
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- Michaels, Thomas C.T. (författare)
- University of Cambridge,Harvard University
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- Cohen, Samuel I.A. (författare)
- University of Cambridge
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- Linse, Sara (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Dobson, Christopher M. (författare)
- University of Cambridge
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- Knowles, Tuomas P.J. (författare)
- University of Cambridge
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- Vendruscolo, Michele (författare)
- University of Cambridge
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(creator_code:org_t)
- 2018-09-26
- 2018
- Engelska 6 s.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:41, s. 10245-10250
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.pnas.org...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure.activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers. We use this estimate to derive chemical rules in the case of the amyloid beta peptide (Aβ), which we then exploit to optimize starting compounds to curtail Aâ oligomer formation. We demonstrate this approach by converting an inactive rhodanine compound into an effective inhibitor of Aβ oligomer formation by generating chemical derivatives in a systematic manner. These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Alzheimer's disease
- Amyloid beta peptide
- Chemical kinetics
- Protein aggregation
- Protein misfolding
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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