Synthesis of amyloid β-peptides: Segment condensation of sparingly soluble protected peptides in chloroform-phenol mixed solvent

Amyloid (1-40, 1-42, 3-42, or 1-43) are sparingly soluble proteolytic fragments present as the major constituent of extracellular proteinaceous deposits known as amyloid plaques. Because of the hydrophobic composition of the C-terminal region of , severe solubility problems arise during the synthesis of these peptides due to aggregation. To prevent this, in stepwise solid-phase synthesis, amide backbone protecting groups (e.g., 2-hydroxy-4-methoxybenzyl) were introduced, but this often led to accumulation of amino acid deletion products which can be extremely difficult to separate from the desired peptide. More promising is the segment condensation method, which can be employed to prepare large quantities of peptides without the formation of amino acid deletion products. This procedure, performed in the solution phase, is extremely efficient for synthesizing sparingly soluble peptides if solvent systems that dissolve the protected intermediates are available during the construction of molecules. In the present study, we developed a new solvent system, a mixture of chloroform and phenol, for the segment condensation of sparingly soluble protected peptides in solution and successfully used it to synthesize and [1].