Second pass at: Where impurities in solid-phase peptide synthesis come from

Second pass at: Where impurities in solid-phase peptide synthesis come from Writing it up because I had to work it out twice and would rather nobody else did.

Impurities in solid-phase peptide synthesis, from the point of view of someone who has read the documentation and is still stuck.

Saying which parts I have understood so that nobody wastes time re-explaining them, and where exactly the understanding stops.

Fine by me. I had wanted a stronger conclusion and there is not one available.

Taking the opening post at face value and following it one step further.

Truncation products: fragments from incomplete synthesis or from degradation. They elute quite differently from the intact peptide because they are much smaller and have different hydrophobicity. They are usually well separated.

I read the opening post twice before replying, because I had assumed the opposite.

Reporting thresholds matter: below a stated threshold, peaks are usually not reported at all. A clean-looking table may reflect a high threshold rather than a clean synthesis.

Off-target structures: if the sequence synthesis goes wrong, a completely different amino acid can be incorporated. The resulting off-target peptide is a structural isomer with the same mass but a different sequence. No chromatographic purity method detects this without a reference standard.

I would treat that as a working assumption and revisit it.