Despite all the continuous efforts to optimize the SPPS, serious problems have intriguingly persisted. They are mainly related to incomplete aminoacylations during peptide growth caused by chain aggregation inside the bead. In this context, Boc/Bzl or Fmoc/tBu strategy have been compared mainly with regard to chemical side-reactions and aggregation. Our group had recently described an aggregation study using the sequence AAXAA to compare these protocols. In order to follow with this study, the aggregating model sequence XAAAA was analyzed, where the amino acid X is Asn, Asp, Gln or Glu. Initially, solvation properties of low (0.5) and highly (2.3 mmol/g) substituted peptidyl-MBHARs were examined in DMF, NMP and DMSO in a combined swelling-EPR approach. The peptide-resins were examined by applying the low-labeling strategy of the TOAC (2,2,6,6-tetramethypiperidine-N-oxide-4-amino-4-carboxylic) spin probe to avoid spin-spin exchange interaction within beads. The side chain protecting groups Trt, Xan or the natural free carboxyamide to Asn and Gln residues and OcHx, tBu, Bzl groups and the free carboxy group to Asp and Glu residues were used. As expected, more pronounced peptide chain aggregation occurred in the heavily peptide-loaded conditions, however, interesting influence of the amino acid protecting groups were detected. Those peptides containing Asn and Gln residues with Trt protecting groups displayed less mobility in both resins, estimated by the EPR central line-width in DMF, NMP and DMSO. Otherwise, when using Asp and Glu residues in X position, the higher chain mobility was obtained using tBu as protecting group and the lower mobility was found when free amino acid is used. These findings suggest that in peptide containing Glu and Asp residues, the better synthesis protocol is the Fmoc/tBu chemistry due to the increased chain motion detected with this strategy. In the other hand, for Asn and Gln-containing sequences, enhanced mobility are observed with free carboxyamide or when Xan protections are used in the Boc/Bzl protocol in comparison with the Trt protection applied in the Fmoc/tBu protocol.