Drug Development in Conformational Diseases: A Novel Family of Chemical Chaperones that Bind and Stabilise Several Polymorphic Amyloid Structures

PloS One
Marquiza Sablón-CarrazanaMyriam M Altamirano-Bustamante

Abstract

The increasing prevalence of conformational diseases, including Alzheimer's disease, type 2 Diabetes Mellitus and Cancer, poses a global challenge at many different levels. It has devastating effects on the sufferers as well as a tremendous economic impact on families and the health system. In this work, we apply a cross-functional approach that combines ideas, concepts and technologies from several disciplines in order to study, in silico and in vitro, the role of a novel chemical chaperones family (NCHCHF) in processes of protein aggregation in conformational diseases. Given that Serum Albumin (SA) is the most abundant protein in the blood of mammals, and Bovine Serum Albumin (BSA) is an off-the-shelf protein available in most labs around the world, we compared the ligandability of BSA:NCHCHF with the interaction sites in the Human Islet Amyloid Polypeptide (hIAPP):NCHCHF, and in the amyloid pharmacophore fragments (Aβ17-42 and Aβ16-21):NCHCHF. We posit that the merging of this interaction sites is a meta-structure of pharmacophore which allows the development of chaperones that can prevent protein aggregation at various states from: stabilizing the native state to destabilizing oligomeric state and protofilament. Furthermore...Continue Reading

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Citations

Dec 30, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Fernanda Avila-VazquezMyriam M Altamirano-Bustamante
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Mar 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isaac Fernández-GómezMyriam M Altamirano-Bustamante
Aug 18, 2021·The International Journal of Neuroscience·Rimaljot SinghTanzeer Kaur
Sep 15, 2020·ACS Chemical Neuroscience·Francesco TavantiAlfredo Alexander-Katz

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Methods Mentioned

BETA
Circular Dichroism
Atomic
atomic force microscopies
Atomic Force Microscopy
fluorescence
light microscopy
NMR

Software Mentioned

Pymol
AutoDockVina
Vina
Origin
Avogadro
Chimera
Log P
STATISTICA
ACD
Autodock Tools

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