Synthetic modification of peptides hasgained interest as a way of mitigatingthe drawbacks of peptide-based drugs,such as the high metabolism of thesecompounds. The peptides QDFFFKQand QKFFFDQ, based on the modelpeptide RFFFR, have been confirmedto fibrillate in polar solvents. The peptideswere successfully modified withmyristic acid and biphenyl-4-carboxylicacid by in situ carboxylic acid esterificationas an extension of standardsolid phase peptide synthesis. Circulardichroism and fluorescence measurementsindicate that the peptides arestabilised bypi-stacking. AFM measurementsshow a significant increase infibrillation propensity for both peptidesafter modification with myristic acid orbiphenyl-4-carboxylic acid. The significantdecrease in solubility in aqueousenvironments after modification couldprove detrimental for use in pharmaceutics.As such, less hydrophobic moietiesshould be investigated.Synthetic modification of peptides hasgained interest as a way of mitigatingthe drawbacks of peptide-based drugs,such as the high metabolism of thesecompounds. The peptides QDFFFKQand QKFFFDQ, based on the modelpeptide RFFFR, have been confirmedto fibrillate in polar solvents. The peptideswere successfully modified withmyristic acid and biphenyl-4-carboxylicacid by in situ carboxylic acid esterificationas an extension of standardsolid phase peptide synthesis. Circulardichroism and fluorescence measurementsindicate that the peptides arestabilised bypi-stacking. AFM measurementsshow a significant increase infibrillation propensity for both peptidesafter modification with myristic acid orbiphenyl-4-carboxylic acid. The significantdecrease in solubility in aqueousenvironments after modification couldprove detrimental for use in pharmaceutics.As such, less hydrophobic moietiesshould be investigated.