Dipropylamine for 9-Fluorenylmethyloxycarbonyl (Fmoc) Deprotection with Reduced Aspartimide Formation in Solid-Phase Peptide Synthesis

Hippolyte Personne; Thissa N Siriwardena; Sacha Javor; Jean-Louis Reymond

doi:10.1021/acsomega.2c07861

Dipropylamine for 9-Fluorenylmethyloxycarbonyl (Fmoc) Deprotection with Reduced Aspartimide Formation in Solid-Phase Peptide Synthesis

ACS Omega. 2023 Jan 23;8(5):5050-5056. doi: 10.1021/acsomega.2c07861. eCollection 2023 Feb 7.

Authors

Hippolyte Personne¹, Thissa N Siriwardena^{1

2}, Sacha Javor¹, Jean-Louis Reymond¹

Affiliations

¹ Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
² Shanghai Space Peptides Pharmaceutical Co., Ltd., Shanghai 201210, China.

Abstract

Herein, we report dipropylamine (DPA) as a fluorenylmethyloxycarbonyl (Fmoc) deprotection reagent to strongly reduce aspartimide formation compared to piperidine (PPR) in high-temperature (60 °C) solid-phase peptide synthesis (SPPS). In contrast to PPR, DPA is readily available, inexpensive, low toxicity, and nonstench. DPA also provides good yields in SPPS of non-aspartimide-prone peptides and peptide dendrimers.