Problem of aspartimide formation in Fmoc-based solid-phase peptide synthesis using Dmab group to protect side chain of aspartic acid

• Published in: Journal of peptide science Vol. 14; no. 3; pp. 335 - 341
• Main Authors: Ruczyński, JarosŁaw, Lewandowska, Brygida, Mucha, Piotr, Rekowski, Piotr
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2008
• Subjects: Amino Acids - chemistry; aspartic acid; Aspartic Acid - analogs & derivatives; Aspartic Acid - chemistry; aspartimide formation; Chemistry - methods; Dmab; Fluorenes - chemistry; Isoaspartic Acid - chemistry; Peptides - chemical synthesis; Peptides - chemistry; solid-phase peptide synthesis
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.941

The sequence‐dependent, acid‐ or base‐catalysed aspartimide formation is one of the most serious side reactions in solid‐phase synthesis of peptides containing aspartic acid. In the present work, we investigated the susceptibility of 4‐{N‐[1‐(4,4‐dimethyl‐2,6‐dioxocyclohexylidene)‐3‐methylbutyl]amino}benzyl (Dmab), an aspartic acid β‐carboxy side‐chain protecting group, for aspartimide formation. As a model, 15‐amino acid‐residue galanin fragment analogue containing the Asp‐Ala motif was used during Fmoc‐based solid‐phase synthesis. Our study showed a strong tendency of Dmab‐protected peptide to form aspartimide with unusual high efficiency. Furthermore, to investigate the susceptibility of Asp‐Ala motif for aspartimide formation during the synthesis using Asp(ODmab), a 5‐amino acid‐residue galanin fragment LGPDA, different types of resin linkers, variety of Fmoc‐deprotection conditions and coupling methods were applied. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.