Direct Continuous Flow Synthesis of Two Difficult Polypeptides Using β-Cyclodextrins

Szaniszló, Szebasztian and Schlosser, Gitta and Farkas, Viktor and Perczel, András (2024) Direct Continuous Flow Synthesis of Two Difficult Polypeptides Using β-Cyclodextrins. THE JOURNAL OF ORGANIC CHEMISTRY, 89 (24). pp. 18039-18046. ISSN 0022-3263

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Abstract

This study focuses on investigating the use of β-cyclodextrin (β-CyD) derivatives as additives in continuous flow peptide synthesis, with particular emphasis on challenging sequences such as the Jung-Redemann decapeptide and the 42-residue amyloid β polypeptide [Aβ(1–42)]. The efficacy of the OH-free β-CyD and two of its derivatives (Ac-β-CyD and HP-β-CyD) is compared with alternative, state-of-the-art synthetic methods, including the widely used and recently improved pseudoproline monomer technique, e.g., Ser(ΨPro). Our results show that the use of β-CyD as an additive results in a significant (8–19%) increase in the purity of the crude polypeptide compared to that determined by our reference method. The chromatograms determined by LC-MS were deconvoluted to estimate the more precise purity of the crude products, and we found that the improvement is greater when the free OH β-CyD is used and moderate when the acetyl-β-CyD or the 2-hydroxypropyl-β-CyD derivatives are used. We have found that the free CyD gives an improvement comparable to that achieved with the Ser(ΨPro) derivative.

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