Synthetic modification of peptides has
gained interest as a way of mitigating
the drawbacks of peptide-based drugs,
such as the high metabolism of these
compounds. The peptides QDFFFKQ
and QKFFFDQ, based on the model
peptide RFFFR, have been confirmed
to fibrillate in polar solvents. The peptides
were successfully modified with
myristic acid and biphenyl-4-carboxylic
acid by in situ carboxylic acid esterification
as an extension of standard
solid phase peptide synthesis. Circular
dichroism and fluorescence measurements
indicate that the peptides are
stabilised bypi-stacking. AFM measurements
show a significant increase in
fibrillation propensity for both peptides
after modification with myristic acid or
biphenyl-4-carboxylic acid. The significant
decrease in solubility in aqueous
environments after modification could
prove detrimental for use in pharmaceutics.
As such, less hydrophobic moieties
should be investigated.