A5030858191- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Supramolecular Self-Assembly in Materials
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Glycosylation and Glycoproteins Research
- Cholinesterase and Neurodegenerative Diseases
- Chemical Synthesis and Analysis
- Physiological and biochemical adaptations
- Neurobiology and Insect Physiology Research
- Trace Elements in Health
- Cell Adhesion Molecules Research
- Advanced Fluorescence Microscopy Techniques
- DNA and Nucleic Acid Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Peptidase Inhibition and Analysis
- Origins and Evolution of Life
University of Toronto
2010-2024
University Health Network
2003-2018
Princess Margaret Cancer Centre
2001-2018
Ontario Institute for Cancer Research
2006-2017
Cancer Institute (WIA)
2003-2017
Discovery Centre
2011-2016
Canada Research Chairs
2012
Medical Council of Canada
2006
University of Geneva
2003
Scripps Research Institute
1999
Abstract Helix propensities of the amino acids have been measured in alanine‐based peptides absence helix‐stabilizing side‐chain interactions. Fifty‐eight studied. A modified form Lifson‐Roig theory for helix‐coil transition, which includes helix capping (Doig AJ, Chakrabartty A, Klingler TM, Baldwin RL, 1994, Biochemistry 33 :3396‐3403), was used to analyze results. Substitutions were made at various positions homologous helical peptides. Helix‐capping interactions found contribute...
Proteinacious intracellular aggregates in motor neurons are a key feature of both sporadic and familial amyotrophic lateral sclerosis (ALS). These inclusion bodies often immunoreactive for Cu,Zn-superoxide dismutase (SOD1) implicated the pathology ALS. On basis this similar clinical presentation symptoms (fALS) forms ALS, we sought to investigate possibility that there exists common disease-related aggregation pathway fALS-associated mutant SODs wild type SOD1. We have previously shown...
The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal cord motor neurons is a pathological hallmark amyotrophic lateral sclerosis (ALS). Although SOD1 abundant all cells, its half-life far exceeds any other cell type. On the basis premise long protein increases potential for oxidative damage, we investigated effects oxidation on misfolding/aggregation and ALS-associated mutants. Zinc-deficient wild-type mutants were extremely prone to form visible...
Increasing evidence implicates Abeta peptides as neurotoxic agents in Alzheimer's disease. We investigated one possible mechanism of neurotoxicity, namely Abeta-membrane lipid interactions. find that disrupts membranes containing acidic phospholipids. This disruption is greater at slightly pH (characteristic endosomes) than neutral the extracellular space). dependence suggests has capacity to disrupt endosomal and plasma membranes, this could account, least part, for observed effects...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAromatic side-chain contribution to far-ultraviolet circular dichroism of helical peptides and its effect on measurement helix propensitiesAvijit Chakrabartty, Tanja Kortemme, S. Padmanabhan, Robert L. BaldwinCite this: Biochemistry 1993, 32, 21, 5560–5565Publication Date (Print):June 1, 1993Publication History Published online1 May 2002Published inissue 1 June...
Amyloid-β (Aβ) assembly into fibrillar structures is a defining characteristic of Alzheimer's disease that initiated by conformational transition from random coil to β-sheet and nucleation-dependent aggregation process. We have investigated the role organic osmolytes as chemical chaperones in amyloid pathway using glycerol mimic effects naturally occurring molecules. Osmolytes such trimethylamine <i>N</i>-oxide correct folding defects preferentially hydrating partially denatured proteins...
Abstract The helix propagation and N‐cap propensities of the amino acids have been measured in alanine‐based peptides 40 volume percent trifluoroethanol (40% TFE) to determine if this helix‐stabilizing solvent uniformly affects all acids. 40% TFE are compared with revised values parameters water. Revision water is result redefining capping statistical weights evaluating nucleation constant N‐capping explicitly included helix‐coil model. increase relative water, but increases highly variable....
Helix content of peptides with various uncharged nonaromatic amino acids at either the N-terminal or C-terminal position has been determined. The choice acid a major effect on helix stability: asparagine is best, glycine very good, and glutamine worst helix-stabilizing this position. rank order stabilization parallels frequencies these boundary (N-cap) helices in proteins found by Richardson [Richardson, J. S. & Richardson, D. C. (1988) Science 240, 1648-1652], peptide composed...
Increasing evidence suggests that Alzheimer β‐amyloid peptides (AAPβ) may be toxic agents in disease. We investigated the possibility toxicity result of peptide‐lipid interactions, involving either cell membrane or intracellular vesicular system. The interaction AAPβ‐(1–40), AAPβ‐(1–42), AAPβ‐(9–25) and AAPβ‐(25–35)‐peptides with acidic zwitterionic phospholipids was by means circular dichroism, vesicle disruption lipid‐aggregation assays. These studies were undertaken at peptide...
Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with infectivity (PrP Sc ). Exposure PrP from other mammals can catalyze this conversion. Evidence experimental and accidental transmission of prions suggests that vary in their disease susceptibility: Hamsters mice show relatively high susceptibility, whereas rabbits, horses, dogs low susceptibility. Using novel approach quantify conformational states by circular dichroism...
Alzheimer's disease is characterized pathologically by the presence of neurofibrillary tangles and amyloid plaques. The principal component plaque β-amyloid peptide (Aβ), a 39–43-residue peptide. conformational change required for conversion soluble into fibrils modulated pH, Aβ concentration, addition kinetic thermodynamic enhancers, alterations in primary sequence Aβ. We report here ability gangliosides to induce an α-helical structure thereby diminish fibrillogenesis. Circular dichroism...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of Free Energies N-Capping in .alpha.-Helixes by Modification the Lifson-Roig Helix-Coil Theory To Include N- and C-CappingAndrew J. Doig, Avijit Chakrabartty, Tod M. Klingler, Robert L. BaldwinCite this: Biochemistry 1994, 33, 11, 3396–3403Publication Date (Print):March 22, 1994Publication History Published online1 May 2002Published inissue 22 March 1994https://doi.org/10.1021/bi00177a033RIGHTS & PERMISSIONSArticle...
Genetic studies have implicated the cytosolic juxtamembrane region of Kit receptor tyrosine kinase as an autoinhibitory regulatory domain. Mutations in domain are associated with cancers, such gastrointestinal stromal tumors and mastocytosis, result constitutive activation Kit. Here we elucidate biochemical mechanism this regulation. A synthetic peptide encompassing demonstrates cooperative thermal denaturation, suggesting that it folds autonomous The directly interacted N-terminal...
The antifreeze polypeptide (AFP) from the winter flounder displays partial α‐helix formation at lower temperatures. To investigate relationship between activity and α‐helical structure, we designed then chemically synthesized an AFP analog with enhanced α‐helicity, compared its conformation properties those of native AFP. synthetic was more helical than AFP; however both peptides were identical. peptids displayed a strong pH dependence, which paralleled pH‐induced changes in helix content....