|
DAEFRHDSGYE is the 11-residue N-terminal fragment of the human amyloid-β peptide (Aβ(1–11)), derived from proteolytic processing of the amyloid precursor protein (APP). Although too short to form fibrils by itself, Aβ(1–11) contains the immunodominant B-cell epitope used widely in epitope-based Alzheimer’s disease (AD) vaccine and antibody studies because antibodies directed to this N-terminus bind plaques and oligomers formed by full-length Aβ peptides.
Molecular details
Sequence: DAEFRHDSGYE (Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu). Molecular weight ≈ 1,326 Da (monoisotopic weight for unmodified peptide varies slightly by vendor). The N-terminal Asp (D1) and residues 2–5 form the core motif recognized by several therapeutic monoclonal antibodies (e.g., gantenerumab binds residues ~3–7), while the acidic residues in the first 11 residues also contribute to metal (Cu²⁺/Zn²⁺) coordination studied in Aβ biochemistry.
Functional roles & mechanism
Aβ(1–11) itself is largely non-aggregating, but (a) it represents the primary B-cell epitope that elicits anti-Aβ antibodies capable of recognizing plaques and oligomers, and (b) it can influence the aggregation behavior of longer Aβ species when present in mixtures or as part of multivalent immunogens. Antibodies raised to Aβ(1–11) have been shown to bind multiple Aβ species and, in preclinical models, to reduce plaque burden or alter pathology when used in epitope vaccine constructs. Also, residues within Aβ(1–11) participate in metal binding sites that modulate Aβ solubility and redox chemistry relevant to toxicity.
Applications
• Immunotherapy & vaccines: Aβ(1–11) is the B-cell epitope in multiple vaccine constructs (e.g., Aβ(1–11)-PADRE, (1–11)E2) designed to induce anti-Aβ humoral responses while avoiding autoreactive T cells; several preclinical studies showed robust antibody responses and plaque targeting.
• Antibody/epitope mapping: Synthetic Aβ(1–11) is used to map antibody specificity and to screen monoclonal/polyclonal reagents.
• Biophysical studies: Employed in metal-binding and computational docking studies to dissect antibody-Aβ interactions (e.g., gantenerumab models) and metal coordination effects.
Practical notes
Use high-purity (>95%) synthetic peptide for immunizations and assays; N-terminal free acid (H-DAEFRHDSGYE-OH) is the canonical form. When designing vaccines, couple Aβ(1–11) to carrier/T-cell epitopes (e.g., PADRE or virus-like particles) to drive safe humoral immunity. Interpret antibody reactivity carefully—anti-Aβ(1–11) sera often cross-react with multiple Aβ species.
| 