Pseudoproline Dipeptides

Pseudoproline dipeptides contain oxazoles formed from serine or threonine.  When treated with trifluoroacetic acid (TFA), the oxazoles are converted to serine or threonine. The oxazoles have structural similarities to proline, thus they are named pseudoprolines.

Like proline, the pseudoprolines create a “kink” in the polyamide backbone of peptides.  The kink disrupts the interchain hydrogen bonding responsible for aggregation.  Incorporating pseudoprolines into the peptide sequence enhances the coupling efficiency, and in turn, improves the purity and yield of the peptide. Coupling to pseudoprolines is difficult and coupling yields are usually low.  Thus pseudoprolines are utilized in peptide synthesis as preformed pseudoproline dipeptides and are regularly used on the Activo-P11 Peptide Synthesizer.

Pseudoproline dipeptides are undoubtedly the most powerful tools described to date for enhancing synthetic efficiency in Fmoc solid phase peptide synthesis. They are particularly effective in the synthesis of intractable peptides, long peptides/small proteins, and cyclic peptides, enabling in many cases the production of peptides that otherwise could not be made.

The insertion of a pseudoproline into a sequence disrupts the formation of the secondary structures thought responsible for problems during peptide assembly, leading to better and more predictable acylation and deprotection kinetics, improved yields, purities and solubilities of crude products, and easier HPLC purification with higher product return.

Since the pseudoproline unit is stable in weak acid conditions for example to AcOH/TFE/DCM, peptides prepared on 2-chlorotrityl resins can be isolated with the pseudoproline moiety still in place; this can be particularly advantageous when preparing peptides for use in fragment condensation reactions, as peptides containing pseudoproline residues often exhibit markedly improved solubility properties. Furthermore, peptides containing a C-terminal pseudoproline residue can be coupled without risk of epimerization.

The kink that pseudoproline produce in linear peptides assists in forming cyclized peptides.  Incorporating a pseudoproline is reported to increase the yield of cyclized peptide and to accelerate the cyclization reaction.

Activotec pseudoproline dipeptides are available in bulk quantities.  Please e-mail Activotec at for a bulk quotation.

Available for fast delivery – contact us now to place an order or to request a quotation info@activotec.com or tel: +44 (0)1223 260008