Peptide Solubility Guidelines
Finding the ideal peptide solubility for a given research process is a serious challenge since improper solubilization can result in loss of peptide or failure of the experiment. There are at least three fundamental characteristics involved in selecting a solvent in which to dissolve the peptide before use.
1. The solvent must be capable of dissolving the peptide effectively.
2. The solvent must be compatible with the experimental application.
3. The solvent should not react with or promote degradation of the peptide. Solvents that can be easily removed by lyophilization are also desirable since they allow convenient retrieval of the peptide.
The simplest way to determine whether a given solvent is feasible is to test it by dissolving a minute amount of peptide. However, this may not be practical if the peptide sample is small to begin with.
As a general rule, peptides should first be dissolved in distilled, sterile water, particularly peptides of fewer than five residues. If solubility remains a problem, please try one or more of the following guidelines:
- Sonication usually helps increase solubility.
- Addition of small amounts of diluted (10%) aqueous acetic acid will help dissolve basic peptides. Please use our IP calculator to see whether your peptide shows an overall basic charge.
- Addition of small amounts of aqueous ammonia will help dissolve acidic peptides. Please use our IP calculator to see whether your peptide shows an overall acidic charge.
- It is also recommended that the peptide be dissolved to the highest possible concentration, then diluted with water or buffer to the working concentration. 10 mg/ml is the upper limit for a regular peptide solution. (Note: Add buffer only after the peptide is completely dissolved. Salts may cause aggregation and create further solubility problems.)
- For peptides with extremely low solubility in aqueous solutions, organic solvents, such as DMSO, methanol, or acetonitrile, should be used first.
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