26-O-acyl β-amyloid (1-42) click peptide was successfully synthesized, the β-ester bond in which can be quickly and quantitatively converted to a native Gly25-Ser26 amide bond via a pH-dependent O-N intramolecular acyl migration reaction (t1/2 =1 min, pH 7.4, 37℃) at a hydroxyamino acid residue. Namely, upon this pH-triggered conversion (pH-click), the non-aggregative and water-soluble precursor (click peptide) can produce the monomer with a random-coil structure under physiological conditions (pH 7.4, 37℃). The structure information is as follows.

Scheme 2: β-amyloid (1-42) click peptide Result

Result

• β-amyloid precursor(click peptide) has a water solubility of 15 mg/ml, while it is only 0.14 mg/ml for the native peptide.
• The aggregative property of the peptides reduced significantly.
• The O-acyl moiety was stable under acidic pH.

Scheme 3: HPLC report of purified β-amyloid (1-42) native peptide converted from β-amyloid (1-42) click peptide (precursor)

Scheme 4: HPLC report of purified 26-O-acyl β-amyloid (1-42) click peptide (precursor)