			Home About us Contact

Peptide Aggregation (peptide + aggregation)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Lattice models of peptide aggregation: Evaluation of conformational search algorithms

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2005
Mark T. Oakley
Abstract We present a series of conformational search calculations on the aggregation of short peptide fragments that form fibrils similar to those seen in many protein mis-folding diseases. The proteins were represented by a face-centered cubic lattice model with the conformational energies calculated using the Miyazawa,Jernigan potential. The searches were performed using algorithms based on the Metropolis Monte Carlo method, including simulated annealing and replica exchange. We also present the results of searches using the tabu search method, an algorithm that has been used for many optimization problems, but has rarely been used in protein conformational searches. The replica exchange algorithm consistently found more stable structures then the other algorithms, and was particularly effective for the octamers and larger systems. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1638,1646, 2005 [source]

Rationally designed dehydroalanine (,Ala)-containing peptides inhibit amyloid-, (A,) peptide aggregation

BIOPOLYMERS, Issue 6 2009
Vijayaraghavan Rangachari
Abstract Among the pathological hallmarks of Alzheimer's disease (AD) is the deposition of amyloid-, (A,) peptides, primarily A, (1,40) and A, (1,42), in the brain as senile plaques. A large body of evidence suggests that cognitive decline and dementia in AD patients arise from the formation of various aggregated forms of A,, including oligomers, protofibrils and fibrils. Hence, there is increasing interest in designing molecular agents that can impede the aggregation process and that can lead to the development of therapeutically viable compounds. Here, we demonstrate the ability of the specifically designed ,,,-dehydroalanine (,Ala)-containing peptides P1 (K-L-V-F-,A-I-,A) and P2 (K-F-,A-,A-,A-F) to inhibit A, (1,42) aggregation. The mechanism of interaction of the two peptides with A, (1,42) seemed to be different and distinct. Overall, the data reveal a novel application of ,Ala-containing peptides as tools to disrupt A, aggregation that may lead to the development of anti-amyloid therapies not only for AD but also for many other protein misfolding diseases. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 456,465, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]

Self-Assembly of Amylin(20,29) Amide-Bond Derivatives into Helical Ribbons and Peptide Nanotubes rather than Fibrils

CHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2006
Ronald C. Elgersma
Abstract Uncontrolled aggregation of proteins or polypeptides can be detrimental for normal cellular processes in healthy organisms. Proteins or polypeptides that form these amyloid deposits differ in their primary sequence but share a common structural motif: the (anti)parallel , sheet. A well-accepted approach for interfering with ,-sheet formation is the design of soluble ,-sheet peptides to disrupt the hydrogen-bonding network; this ultimately leads to the disassembly of the aggregates or fibrils. Here, we describe the synthesis, spectroscopic analysis, and aggregation behavior, imaged by electron microscopy, of several backbone-modified amylin(20,29) derivatives. It was found that these amylin derivatives were not able to form fibrils and to some extent were able to inhibit fibril growth of native amylin(20,29). However, two of the amylin peptides were able to form large supramolecular assemblies, like helical ribbons and peptide nanotubes, in which ,-sheet formation was clearly absent. This was quite unexpected since these peptides have been designed as soluble ,-sheet breakers for disrupting the characteristic hydrogen-bonding network of (anti)parallel , sheets. The increased hydrophobicity and the presence of essential amino acid side chains in the newly designed amylin(20,29) derivatives were found to be the driving force for self-assembly into helical ribbons and peptide nanotubes. This example of controlled and desired peptide aggregation may be a strong impetus for research on bionanomaterials in which special shapes and assemblies are the focus of interest. [source]

Tacrine,Melatonin Hybrids as Multifunctional Agents for Alzheimer's Disease, with Cholinergic, Antioxidant, and Neuroprotective Properties

CHEMMEDCHEM, Issue 5 2009
María Isabel Fernández-Bachiller Dr.
Abstract Tacrine,melatonin hybrids are potential multifunctional drugs for Alzheimer's disease that may simultaneously palliate intellectual deficits and protect the brain against both ,-amyloid peptide and oxidative stress. Molecular modeling studies show that they target both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. They are nontoxic and may be able to penetrate the CNS, according to in,vitro PAMPA-BBB assays. Tacrine,melatonin hybrids were designed and synthesized as new multifunctional drug candidates for Alzheimer's disease. These compounds may simultaneously palliate intellectual deficits and protect the brain against both ,-amyloid (A,) peptide and oxidative stress. They show improved cholinergic and antioxidant properties, and are more potent and selective inhibitors of human acetylcholinesterase (hAChE) than tacrine. They also capture free radicals better than melatonin. Molecular modeling studies show that these hybrids target both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. At sub-micromolar concentrations they efficiently displace the binding of propidium iodide from the PAS and could thus inhibit A, peptide aggregation promoted by AChE. Moreover, they also inhibit A, self-aggregation and display neuroprotective properties in a human neuroblastoma line against cell death induced by various toxic insults, such as A,25,35, H2O2, and rotenone. Finally, they exhibit low toxicity and may be able to penetrate the central nervous system according to an in,vitro parallel artificial membrane permeability assay for the blood,brain barrier (PAMPA-BBB). [source]