Biomaterial Database

Measurement of peptide aggregation with pulsed-field gradient nuclear magnetic resonance spectroscopy. 1998

S L Mansfield, and D A Jayawickrama, and J S Timmons, and C K Larive

Department of Chemistry, University of Kansas, Lawrence 66045, USA.

Interactions between hydrophobic patches in proteins are often a driving force for denaturation and aggregation. The aggregation of the beta-amyloid peptide fragment, VHHQKLVFFAEDVGSNK (beta(12-28)), has been investigated in aqueous solution at low pH. This peptide contains a central hydrophobic patch spanning residues 17-21. Diffusion coefficients measured with pulsed-field gradient NMR as a function of peptide solution concentration were used to assess the extent of aggregation. Following the hypothesis that hydrophobic interactions are an important driving force in the aggregation of this peptide at low pH, a non-aggregating analog of the beta(12-28) peptide, [Gly19,20]beta(12-28) was synthesized. In the [Gly19,20]beta(12-28) peptide, the replacement of the two phenylalanine residues disrupts the hydrophobic interactions which drive the aggregation of beta(12-28). The diffusion coefficient of the [Gly19,20]beta(12-28) peptide is invariant over the concentration range studied and provides a good estimate of the monomeric diffusion coefficient of beta(12-28). A second peptide analog was synthesized in which the phenylalanine at position 20 was replaced with a cysteine residue. The disulfide-linked dimer, ([Cys20]beta(12-28))2, was formed upon air oxidation of this peptide. The diffusion coefficient of the ([Cys20]beta(12-28))2 peptide was measured and used to estimate the diffusion coefficient of the beta(12-28) dimer. Using the monomeric and dimeric diffusion coefficients measured for the glycine and cysteine analogs, the concentration dependence of the beta(12-28) diffusion coefficient was found to be consistent with a monomer-dimer aggregation model.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D004058	Diffusion	The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT.	Diffusions
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D016229	Amyloid beta-Peptides	Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.	Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D019281	Dimerization	The process by which two molecules of the same chemical composition form a condensation product or polymer.	Dimerizations
D019906	Nuclear Magnetic Resonance, Biomolecular	NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.	Biomolecular Nuclear Magnetic Resonance,Heteronuclear Nuclear Magnetic Resonance,NMR Spectroscopy, Protein,NMR, Biomolecular,NMR, Heteronuclear,NMR, Multinuclear,Nuclear Magnetic Resonance, Heteronuclear,Protein NMR Spectroscopy,Biomolecular NMR,Heteronuclear NMR,Multinuclear NMR,NMR Spectroscopies, Protein,Protein NMR Spectroscopies,Spectroscopies, Protein NMR,Spectroscopy, Protein NMR