Charge
Ionisable side chains gain or lose protons as pH changes. That determines the net charge on the molecule, which in turn determines solubility, chromatographic behaviour and in many cases binding.
Degradation rate
Different degradation routes have different pH dependencies. Hydrolysis of the backbone is accelerated at both acidic and alkaline extremes. Deamidation of asparagine and glutamine accelerates markedly as pH rises above neutral. Disulfide scrambling is also base-catalysed.
Because these have different profiles, there is no universally optimal pH — only one that balances the routes most relevant to a given sequence. For many peptides that falls in the mildly acidic range.
Why it matters at reconstitution
The solvent sets the pH of the resulting solution. Choosing a solvent is therefore also choosing a degradation profile, which is part of why compatibility is documented per compound rather than assumed.
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