Amyloid β-Protein (31-42)

Amyloid Beta 42 C-terminal (31-42), sequence IIGLMVGGVVIA, corresponds to the highly hydrophobic C-terminal domain of human amyloid-β42 (Aβ42). This region plays a central role in amyloid self-assembly, oligomer formation, membrane interaction, and fibril maturation, making it one of the most extensively investigated domains in Alzheimer's disease research.

Compared with the corresponding Aβ(31-40) fragment, the Aβ(31-42) sequence contains the additional residues Ile41 and Ala42. Numerous structural and biochemical studies have demonstrated that these two C-terminal residues dramatically increase peptide hydrophobicity, stabilize intermolecular interactions, accelerate fibril nucleation, and contribute to the enhanced neurotoxicity of Aβ42 compared with Aβ40.

Scientific Background

Amyloid-β42 is widely regarded as the most aggregation-prone and pathogenic form of amyloid-β. The extreme C-terminal region (residues 31-42) forms the hydrophobic core of amyloid fibrils and contributes to the formation of soluble oligomers that are believed to be major neurotoxic species in Alzheimer's disease.

Cryo-electron microscopy, solid-state NMR, molecular dynamics simulations, and X-ray structural studies have consistently shown that residues 31-42 participate directly in intermolecular packing within amyloid fibrils. The hydrophobic interactions formed by Ile31, Leu34, Met35, Val36, Val39, Val40, Ile41, and Ala42 stabilize β-sheet-rich fibrillar assemblies and promote self-association.

Importance of the Aβ42 C-terminal Region

The two additional amino acids present in Aβ42 (Ile41 and Ala42) distinguish Aβ42 from Aβ40 and are considered major determinants of Alzheimer's disease pathology.

• Increase hydrophobic interactions between peptide molecules
• Accelerate oligomer formation
• Promote β-sheet stabilization
• Enhance fibril nucleation kinetics
• Increase membrane affinity
• Contribute to neuronal toxicity

Because of these unique structural properties, short peptides encompassing the C-terminal hydrophobic domain have become valuable experimental models for investigating amyloid aggregation mechanisms without requiring the full-length 42-residue peptide.

Applications in Alzheimer's Disease Research

• Amyloid aggregation studies
• Fibril nucleation research
• Hydrophobic peptide self-assembly
• β-sheet formation analysis
• Amyloid oligomer characterization
• Membrane-peptide interaction studies
• Structure-function relationship investigations
• Small-molecule aggregation inhibitor screening

Mechanistic Features

Hydrophobic Core of Amyloid β42
The peptide represents the hydrophobic C-terminal core responsible for intermolecular packing during fibril formation and amyloid self-assembly.

β-sheet Formation
The sequence readily adopts β-sheet-rich conformations under aggregation-promoting conditions, making it an excellent model peptide for structural biology and aggregation studies.

Membrane Association
Due to its highly hydrophobic nature, this peptide has been widely used to investigate interactions between amyloid peptides and lipid membranes, an important component of amyloid-induced cellular toxicity.

Aggregation Nucleation
The C-terminal residues of Aβ42 are considered critical nucleation elements that initiate oligomer formation and fibril growth, making this peptide highly relevant for mechanistic studies of Alzheimer's disease.

Experimental Applications

Researchers commonly employ this fragment in:

• Circular dichroism (CD) spectroscopy
• Solid-state and solution NMR
• Cryo-electron microscopy
• Transmission electron microscopy (TEM)
• Thioflavin T aggregation assays
• Dynamic light scattering (DLS)
• Surface plasmon resonance (SPR)
• Molecular dynamics simulations

Handling and Solubilization

Because the peptide is extremely hydrophobic, careful solubilization is recommended before use. Many researchers initially dissolve the peptide in HFIP or DMSO prior to dilution into experimental buffers. Proper handling helps minimize uncontrolled aggregation and improves experimental reproducibility.

For additional recommendations, please refer to our Amyloid Peptides for Alzheimer's Disease Research resource page and our Amyloid Peptide Solubilization Guide.

Related Products

Beta-Amyloid (1-42), Human
Beta-Amyloid (1-40), Ultra Pure
Amyloid Peptide Category
Amyloid Research Resource Center

Research Use Only. Not for human or therapeutic use.

Amyloid β-Protein (31-42) is a synthetic amyloid-beta (Aβ) research peptide. Amyloid-beta peptides are proteolytic products of amyloid precursor protein. Sequence length and residue composition strongly influence aggregation: Aβ42 generally aggregates more rapidly than Aβ40, and C-terminal fragments containing residues in the 34-42 region can adopt stable beta-structure. Truncated, reverse-sequence, isotopically labeled, or chemically modified Aβ constructs are therefore best interpreted as distinct research reagents rather than assumed equivalents of native Aβ40 or Aβ42.

• amyloid aggregation and fibrillization studies
• LC-MS/HPLC analytical reference work
• Aβ sequence-length and modification comparisons
• antibody, binding, and assay controls

The exact sequence, phosphorylation state, residue numbering, terminal modifications, labels, and species context should be matched to the intended assay. Sequence motifs support experimental interpretation but do not by themselves establish absolute enzyme specificity or native biological activity.

1. Sequence determinants of enhanced amyloidogenicity of Aβ42 relative to Aβ40
2. Molecular determinants of amyloid deposition: synthetic beta-protein fragments
3. Impact of sequence on assembly of short amyloid peptides