posted on 2023-06-07, 17:36authored bySzebasztián Szaniszló, Kristóf Ferentzi, András Perczel, Viktor Farkas
Pseudoproline
derivatives are incorporated into polypeptides as
aggregation disrupters during synthesis, from which the unmodified
side chains can be recovered during the final step (resin cleavage).
However, direct coupling to pseudoproline is challenging and thus
dipeptides of pseudoproline, Fmoc-Xaa-Yaa(ΨMe,Mepro)-OH,
are traditionally introduced, which requires the entire library of
Fmoc-Xaa-Thr(ΨMe,Mepro)-OH in stock, making this
approach expensive. Here, we show how the in situ acylation of the
incorporated H-Thr(ΨPro)– can be done successful in flow
peptide chemistry, with almost all proteinogenic amino acids (Xaa
or X). The Xaa-Thr(ΨPro) amide bond was established with a reagent
excess of three to five equivalents, with better than 75% efficiency
for most Xaa and 70% in the case of Met. Only for Asp was the efficiency
too low (8%) to support the direct use of pseudoproline derivatives.