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Peptide Solubility

    The first solvent of choice is deionized water. Sonication may help to dissolve the peptide.
The majority of peptides are soluble in water, either alone or buffered with acid (for example, acetic acid) or base (for example, ammonium carbonate). A peptide is likely to have the minimum solubility at a pH that is similar to its isoelectric point and becomes more soluble as the pH varies from this value. Thus, peptides with an excess of basic residues (Arg, Lys, His) will tend to be more soluble at acid pH, whereas peptides with an excess of acidic residues (Asp, Glu) will tend to be more soluble at higher pH. Care should be taken not to expose the peptide to extremes of pH as these are likely to cause damage.

   Basic peptides containing predominantly basic residues (Arg, Lys, His): 10% acetic acid or 0.1% TFA (trifluoroacetic acid) will increase the solubility. Increase the concentration of the acid stepwise if the peptide does not dissolve.
Acidic peptides containing predominantly acidic residues (Asp, Glu): 1% ammonium hydroxide or 10% ammonium bicarbonate will help to solubilize the peptide.
Hydrophobic (Trp, Phe, Leu, Ile, Met, Val and Tyr) or neutral peptides: Stepwise addition of acetonitrile, isopropanol, DMF or DMSO (from 5 to 50%). Please note that these solvents may have a damaging effect on your experiments. For peptides with secondary structures, it may be necessary to add chaotropic agents such as urea or guanidium-HCl.
Special care should be exercised when dissolving peptides that contain cysteines as these can be very easily oxidized. The tendency of cysteine containing peptides to oxidize can be reduced by dissolving them in water buffered with 0.1%v/v trifluoroacetic acid or by adding a reagent such as dithiothreitol to prevent disulphide formation.



    For maximum stability we recommend storing the lyophilized peptide at -20°C. Peptides in solution should be aliquoted and stored at -20°C to avoid repeated freeze-thaw cycles. Hygroscopic peptides should be brought to room temperature before the vial is opened. The vial should be re-sealed as soon as possible to prevent absorption of water from the atmosphere.
    Peptides containing Trp, Met and Cys are susceptible to oxidation and should be stored under nitrogen or argon. Solutions of these peptides should be degassed and stored at -70°C. We recommend the same procedure for peptides containing Gln and Asn which are prone to deamidation.