Poster Presentation 9th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2023

Backbone protecting groups for improving Fmoc SPPS (#110)

Samuel J Paravizzini 1 , Craig A Hutton 1 , John A Karas 1
  1. The University of Melbourne, Parkville, VIC, Australia

The use of backbone protecting groups during 9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS) is an effective strategy for improving synthetic yields and the quality of the crude product.1 These acid-labile protecting groups increase the solubility of the growing peptide chain and suppress chain aggregation which can cause poor reaction kinetics during assembly.2,3 Existing approaches include the use of pseudo-proline dipeptides; however, their usage is limited to serine, threonine, and cysteine residues.4,5 Benzyl-based protecting groups are an alternative and can be conveniently introduced in situ; unfortunately, they can be difficult to remove during trifluoroacetic acid deprotections, and the reactive benzyl cations that are generated can covalently modify the target peptide.6,7 This research seeks to develop new backbone protection strategies that are amenable to Fmoc SPPS protocols. Each protecting group that is under investigation has undergone rigorous evaluation and has been benchmarked against the dicyclopropylmethyl (Dcpm) group, reported by Carpino et al.8 Ultimately, this work promises to address the limitations of Fmoc SPPS and will enable ready access to longer peptides for drug discovery and large scale peptide synthesis.  64b790baf0d8c-img.jpg

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