[Asn7]-beta-Amyloid (1-42), Tottori-Japanese Mutation

Product Name: [Asn7]-beta-Amyloid (1-42), Tottori-Japanese Mutation

Sequence One Letter Code: DAEFRHNSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA

Sequence Three Letter Code: H-Asp-Ala-Glu-Phe-Arg-His-Asn-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala-OH

Chemical Formula:C203H312N56O59S

Molecular Weight: 4513.4

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: [Asn7]-β-Amyloid (1–42) is a synthetic peptide carrying the D7N (Tottori-Japanese) familial Alzheimer’s disease mutation. This substitution alters aggregation dynamics by selectively enhancing fibril elongation and increasing neurotoxicity. The peptide promotes formation of toxic amyloid assemblies and is widely used to study mutation-dependent aggregation kinetics and structure–toxicity relationships. It supports investigations into early-onset Alzheimer’s disease, amyloid fibrillogenesis, and neuronal injury mechanisms linked to pathogenic β-amyloid variants.

Current Research: [Asn7]-β-Amyloid (1–42) is a synthetic peptide incorporating the D7N substitution, also known as the Tottori-Japanese mutation, associated with autosomal dominant early-onset Alzheimer’s disease (AD). This point mutation replaces aspartic acid at position 7 with asparagine within the N-terminal region of the Aβ1–42 sequence. Although located outside the central hydrophobic core traditionally linked to aggregation, the D7N substitution significantly alters amyloid assembly kinetics and enhances neurotoxic potential. As such, [Asn7]-Aβ(1–42) serves as a valuable model for investigating mutation-dependent modulation of amyloid fibrillogenesis and pathogenicity. Residue 7 lies within the N-terminal segment of Aβ, a region involved in metal ion binding, electrostatic interactions, and early conformational transitions preceding fibril formation. Substitution of negatively charged aspartate with neutral asparagine modifies local hydrogen bonding capacity and reduces electrostatic repulsion within assembling peptides. Experimental studies indicate that the D7N mutation selectively enhances fibril elongation rather than dramatically accelerating primary nucleation. This distinction provides insight into how specific amino acid changes influence discrete steps within the aggregation pathway. Biophysical analyses of [Asn7]-Aβ(1–42) commonly employ thioflavin T fluorescence assays to monitor β-sheet formation and fibril growth kinetics. Compared with wild-type Aβ1–42, the D7N variant demonstrates increased elongation rates and a greater propensity to generate stable fibrillar structures. Circular dichroism spectroscopy confirms accelerated transition to β-sheet–rich conformations, while transmission electron microscopy reveals dense fibril networks with defined morphology. These properties make the peptide particularly useful for dissecting elongation-phase dynamics in amyloid assembly. The mutation’s impact on toxicity is of significant interest. Oligomeric intermediates derived from Aβ variants are widely regarded as key mediators of synaptic dysfunction and neuronal injury. [Asn7]-Aβ(1–42) has been shown to promote formation of assemblies with enhanced cytotoxicity in cultured neuronal models. These toxic species can disrupt membrane integrity, induce calcium influx, promote oxidative stress, and activate apoptotic pathways. Comparative studies between wild-type and D7N peptides clarify how subtle structural alterations translate into differential neurotoxic outcomes. The D7N mutation also provides a framework for studying structure–toxicity relationships. High-resolution structural techniques, including solid-state NMR and molecular dynamics simulations, are used to examine how the substitution influences β-strand alignment, hydrogen-bonding patterns, and protofilament packing. Altered intermolecular interactions may stabilize specific fibril polymorphs or oligomeric conformations with increased pathogenic potential. Understanding these structural consequences helps explain the clinical severity observed in familial AD cases carrying the Tottori mutation. In addition, [Asn7]-Aβ(1–42) is employed to explore interactions with metal ions such as copper and zinc, which bind within the N-terminal domain and modulate aggregation behavior. Because the D7N substitution modifies the local charge environment, it may influence metal coordination and redox activity, thereby affecting oxidative stress mechanisms implicated in AD pathology. From a translational perspective, the D7N variant serves as a stringent model for evaluating aggregation inhibitors and conformation-selective antibodies. Compounds capable of attenuating fibril elongation or destabilizing toxic assemblies in this aggressive mutant context may hold therapeutic relevance for hereditary forms of AD. Screening studies often compare inhibitor efficacy against wild-type and mutant peptides to assess mutation-specific responses. In summary, [Asn7]-β-Amyloid (1–42) represents a familial Alzheimer’s disease–associated variant that enhances fibril elongation and increases neurotoxicity. By altering early aggregation dynamics and structural stability, the D7N mutation provides critical insight into mutation-driven amyloid pathogenesis. This peptide remains an essential research tool for investigating early-onset AD mechanisms, aggregation kinetics, and the molecular basis of mutation-linked neuronal injury.