Consider the synthesis of the dipeptide Glu–Ala (image). The amino acid Glu (glutamic acid) has two carboxyl groups, where one of them should reacts with the amine group from the other amino acid. Does the side chain carboxyl group in Glu have to be protected also, or do we just assume that it does not react?
Yes, the side chain carboxylic acid requires protection.
The two most commonly used peptide coupling strategies use Boc or Fmoc on the amide.
The side-chain carboxylate is typically protected as a tBu ester in case of Fmoc synthesis (the compound is commercially available under CAS 71989-18-9) or as a benzyl ester in case of Boc synthesis (as before, CAS 13574-13-5).
Not protecting these side chains would give coupling mixtures as both carboxylic acids can and will react with the coupling reagents.