Problem of aspartimide formation in Fmoc-based solid-phase peptide synthesis using Dmab group to protect side chain of aspartic acid.
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 beta-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.
Ruczyński
Jarosław
J
Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. jarecki@chem.univ.gda.pl
Lewandowska
Brygida
B
Mucha
Piotr
P
Rekowski
Piotr
P
D000596:Amino Acids / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D002621:Chemistry / Q000379:methods; D005449:Fluorenes / Q000737:chemistry*; D026581:Isoaspartic Acid / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
D000596:Amino Acids; D005449:Fluorenes; D026581:Isoaspartic Acid; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D001224:Aspartic Acid; C075871:aspartimide