The preferred solvent for most peptides is ultrapure pumping water. Dilute acetic acid or aqueous ammonia is important for the dissolution of basic or acidic polypeptides respectively. For peptides that are not soluble in these methods, DMF, urea, guanidiniam chloride or acetonitrnle are required for dissolution, but these solvents may have side effects in some experiments. So we suggest paying more attention when designing peptides.
Residues Ala, Cys, Ile, Leu, Met, Phe and Val will all increase the difficulty of solubility of the polypeptide.
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