ArticleBioinformatics (Oxford, England)2015
Probing the binding affinity of amyloids to reduce toxicity of oligomers in diabetes.
Article in Bioinformatics (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Bioinformatics Methods in Predicting Amyloid Propensity of Peptides and Proteins.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Microcanonical insights into the physicochemical stability of the coformulation of insulin with amylin analogues.Journal of molecular modeling · 2021Article
- Diabetes Drug Discovery: hIAPPMolecules (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
motivationAmyloids play a role in the degradation of β-cells in diabetes patients. In particular, short amyloid oligomers inject themselves into the membranes of these cells and create pores that disrupt the strictly controlled flow of ions through the membranes. This leads to cell death. Getting rid of the short oligomers either by a deconstruction process or by elongating them into longer fibrils will reduce this toxicity and allow the β-cells to live longer.
resultsWe develop a computational method to probe the binding affinity of amyloid structures and produce an amylin analog that binds to oligomers and extends their length. The binding and extension lower toxicity and β-cell death. The amylin analog is designed through a parsimonious selection of mutations and is to be administered with the pramlintide drug, but not to interact with it. The mutations (T9K L12K S28H T30K) produce a stable native structure, strong binding affinity to oligomers, and long fibrils. We present an extended mathematical model for the insulin-glucose relationship and demonstrate how affecting the concentration of oligomers with such analog is strictly coupled with insulin release and β-cell fitness. AVAILABILITY AND IMPLEMENTATION: SEMBA, the tool to probe the binding affinity of amyloid proteins and generate the binding affinity scoring matrices and R-scores is available at: http://amyloid.cs.mcgill.ca
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Registered trials
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