The Amino Acids Physical Properties table can be used collectively to analyze an individual amino acid’s effect on a peptide’s overall solubility. By considering charge, hydropathy, and the presence of free terminal alpha residues, solubility can be predicted with more consistent accuracy. Peptides should always be solubility tested before large-scale solubility is attempted.
Keep in mind that charge can also greatly effect solubility. To minimize any problems, there should be a balance of negative (acid) and positive (basic) amino acids. If problems are encountered, always add up total pKs (included side chains), and add the appropriate amount of base or acid to the buffer.
When a peptide contains 65% or greater hydrophilic residues, solubility is usually assured unless there the peptide is weighted. Weighting can involve the presence of all hydrophobic residues on one side of the peptide, multiple difficult contiguous structural residues, or extreme charge on one side or region within the peptide. The follow examples apply as where underlined.
Peptide 1: WYIILPDRSTPYLEDN
Peptide 2: GHILDEIPVVYWRSK
Peptide 3: RRKRESTGHILDEKN
Peptide 4: EEDPTYDEQPMEDEE