[Arg6]-beta-Amyloid (1-42), English Mutation

Product Name: [Arg6]-beta-Amyloid (1-42), English Mutation

Sequence One Letter Code: DAEFRRDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA

Sequence Three Letter Code: H-Asp-Ala-Glu-Phe-Arg-Arg-Asp-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:C203H316N56O60S

Molecular Weight: 4533.5

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: This peptide represents β-amyloid (1–42) carrying the English familial mutation, in which histidine at position 6 is substituted with arginine (H6R). This mutation has been shown to accelerate fibril elongation kinetics without markedly increasing protofibril accumulation, providing a defined model for studying mutation-driven aggregation dynamics. The peptide is valuable for dissecting molecular determinants of amyloid assembly, fibril growth mechanisms, and structure–toxicity relationships. It is widely applied in Alzheimer’s disease research to investigate familial amyloid pathology, aggregation kinetics, and the impact of sequence variation on amyloidogenic behavior.

Current Research: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptides in the brain, where they aggregate into soluble oligomers and insoluble fibrillar deposits. While most Alzheimer’s cases occur sporadically, a number of familial mutations in the amyloid precursor protein (APP) gene alter the sequence of amyloid-β peptides and influence their aggregation behavior. These mutations provide valuable insights into how small sequence changes affect amyloid formation and neurotoxicity. One such variant is the β-amyloid (1–42) peptide carrying the English familial mutation (H6R), in which histidine at position 6 is replaced by arginine. This mutant peptide serves as a powerful experimental model for studying mutation-driven aggregation dynamics and amyloid assembly mechanisms. Amyloid-β and Alzheimer’s Disease Pathology Amyloid-β peptides are produced through sequential cleavage of the amyloid precursor protein (APP) by β-secretase and γ-secretase enzymes. The resulting peptides typically range from 38 to 43 amino acids in length, with Aβ40 and Aβ42 being the most common forms. Among these, Aβ42 is particularly prone to aggregation because of its hydrophobic C-terminal residues. This peptide readily forms oligomers, protofibrils, and fibrillar aggregates that accumulate as extracellular plaques in the brains of individuals with Alzheimer’s disease. Increasing evidence suggests that the aggregation pathway and structural transitions of amyloid peptides play critical roles in disease progression. Studying how sequence variations influence these processes helps clarify the molecular origins of amyloid pathology. The English Familial Mutation (H6R) The English familial mutation involves substitution of histidine at position 6 with arginine (H6R) in the amyloid-β sequence. This mutation occurs near the N-terminal region of the peptide, a segment involved in early intermolecular interactions and aggregation initiation. Although the mutation does not dramatically change the overall structure of the peptide, it alters local charge distribution and hydrogen-bonding potential. These changes can influence how individual peptides interact during the early stages of aggregation. Mutations in the amyloid sequence provide valuable systems for studying how specific amino acid substitutions modify aggregation kinetics and structural stability. Effects on Amyloid Aggregation Kinetics Studies of the H6R mutant have shown that this substitution can accelerate fibril elongation kinetics, meaning that fibril growth occurs more rapidly once aggregation begins. Interestingly, this enhanced fibril formation does not appear to significantly increase the accumulation of intermediate protofibrils. This behavior suggests that the mutation may favor direct conversion of monomeric or small oligomeric species into fibrillar structures, bypassing prolonged accumulation of intermediate assemblies. Such observations help clarify the distinct stages of amyloid assembly, including nucleation, oligomer formation, and fibril elongation. Investigating Molecular Determinants of Amyloid Assembly The H6R mutant peptide provides a controlled model for investigating the molecular determinants that govern amyloid assembly. By comparing the aggregation behavior of the mutant peptide with that of the wild-type Aβ42 sequence, researchers can identify how subtle changes in sequence composition affect intermolecular interactions. Experimental approaches such as fluorescence assays, electron microscopy, and structural spectroscopy are often used to examine how the mutation influences fibril morphology, aggregation kinetics, and peptide conformation. These studies help clarify how specific residues within the amyloid sequence contribute to β-sheet formation and fibrillar architecture. Studying Structure–Toxicity Relationships Another important application of the H6R mutant peptide is the investigation of structure–toxicity relationships in amyloid assemblies. Different structural forms of amyloid peptides—such as oligomers, protofibrils, and mature fibrils—can exhibit different biological activities. Some soluble oligomeric forms are believed to be particularly harmful to neuronal cells, disrupting synaptic signaling and membrane integrity. By studying mutants that alter aggregation pathways, researchers can determine how changes in peptide sequence influence the formation of these toxic assemblies. Understanding how specific mutations affect amyloid structure helps reveal the connection between aggregation behavior and neurotoxicity. Relevance to Familial Alzheimer’s Disease Familial mutations in the amyloid-β sequence provide important clues about the molecular basis of inherited forms of Alzheimer’s disease. The H6R mutation serves as an example of how even minor sequence variations can alter peptide behavior and potentially influence disease progression. Studying such mutations allows researchers to examine how genetic alterations affect amyloid formation, stability, and pathogenic potential. Insights gained from these models contribute to a broader understanding of how amyloid aggregation contributes to neurodegeneration. Applications in Alzheimer’s Disease Research Because of its well-defined effects on aggregation kinetics, the Aβ (1–42) H6R mutant peptide is widely used in Alzheimer’s disease research. It provides a valuable system for investigating the mechanisms of amyloid assembly, fibril growth, and mutation-driven structural changes. Researchers use this peptide in experiments focused on aggregation kinetics, structural characterization, and evaluation of molecules that influence amyloid formation. These studies help identify factors that modulate amyloid behavior and may inform strategies for targeting amyloid aggregation in therapeutic research. Conclusion The β-amyloid (1–42) peptide carrying the H6R English familial mutation provides a well-defined experimental model for studying how sequence variations influence amyloid aggregation. By accelerating fibril elongation without significantly increasing protofibril accumulation, the mutation offers insight into the mechanisms governing amyloid assembly. Through applications in aggregation kinetics studies, structural analysis, and investigations of amyloid toxicity, this peptide supports research aimed at understanding the molecular processes underlying familial Alzheimer’s disease and the broader biology of amyloid formation.