Abstract: The formation of inactive, insoluble forms of peptide can be minimized or, alternatively, inactive, insoluble forms of peptide compounds, if present, can be converted into more physiologically active, soluble forms by dissolving peptide samples in aqueous base and then acidifying the aqueous mixture to precipitate the peptide in the presence of at least one of a salt and a co-solvent. Preferably, both a salt and co-solvent are present. By carrying out the precipitation relatively rapidly (at least in a first stage of acidifying in which the pH of the alkaline medium is reduced to a pH in the range of 6 to 7.5, after which acidification to a final desired pH, e.g., 3 to 6, can occur more slowly) at relatively low temperature, the dissolution characteristics of the resultant precipitated peptide are even further improved. The process is robust, consistent, and suitable for commercial scale manufacture of peptides.

Abstract: The invention provides methods for synthesizing peptides, which include taking an organic solvent having non-resin bound protected peptide and performing a deprotection reaction on the non-resin bound protected peptide. In these methods it is not required that the peptide is dried immediately before providing to the deprotection reaction. Also provided are methods of synthesizing peptides, wherein a protected peptide is formed in a solution phase reaction, dissolved into an organic solvent, and then introduced into a deprotection reaction. Also provided are methods of synthesizing peptides, wherein a non-resin bound protected peptide is concentrated in an organic solvent prior to being subject to a deprotection reaction.