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BMC Pharmacol Toxicol. 2014 Feb 27;15:9. doi: 10.1186/2050-6511-15-9.

Modeling of chemical inhibition from amyloid protein aggregation kinetics.

Author information

1
Grupo de Reciclado e Valorización de Residuos (REVAL), Instituto de Investigacións Mariñas (IIM-CSIC), C/ Eduardo Cabello 6, CP36208 Vigo, Spain. jvazquez@iim.csic.es.

Abstract

BACKGROUNDS:

The process of amyloid proteins aggregation causes several human neuropathologies. In some cases, e.g. fibrillar deposits of insulin, the problems are generated in the processes of production and purification of protein and in the pump devices or injectable preparations for diabetics. Experimental kinetics and adequate modelling of chemical inhibition from amyloid aggregation are of practical importance in order to study the viable processing, formulation and storage as well as to predict and optimize the best conditions to reduce the effect of protein nucleation.

RESULTS:

In this manuscript, experimental data of insulin, Aβ42 amyloid protein and apomyoglobin fibrillation from recent bibliography were selected to evaluate the capability of a bivariate sigmoid equation to model them. The mathematical functions (logistic combined with Weibull equation) were used in reparameterized form and the effect of inhibitor concentrations on kinetic parameters from logistic equation were perfectly defined and explained. The surfaces of data were accurately described by proposed model and the presented analysis characterized the inhibitory influence on the protein aggregation by several chemicals. Discrimination between true and apparent inhibitors was also confirmed by the bivariate equation. EGCG for insulin (working at pH = 7.4/T = 37°C) and taiwaniaflavone for Aβ42 were the compounds studied that shown the greatest inhibition capacity.

CONCLUSIONS:

An accurate, simple and effective model to investigate the inhibition of chemicals on amyloid protein aggregation has been developed. The equation could be useful for the clear quantification of inhibitor potential of chemicals and rigorous comparison among them.

PMID:
24572069
PMCID:
PMC3939820
DOI:
10.1186/2050-6511-15-9
[Indexed for MEDLINE]
Free PMC Article
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