title: New t-butyl based aspartate protecting groups preventing aspartimide formation in Fmoc SPPS.
abstract: Obtaining homogenous aspartyl-containing peptides via Fmoc/tBu chemistry is often an insurmountable obstacle. A generic solution for this issue utilising an optimised side-chain protection strategy that minimises aspartimide formation would therefore be most desirable. To this end, we developed the following new derivatives: Fmoc-Asp(OEpe)-OH (Epe = 3-ethyl-3-pentyl), Fmoc-Asp(OPhp)-OH (Php = 4-n-propyl-4-heptyl) and Fmoc-Asp(OBno)-OH (Bno = 5-n-butyl-5-nonyl). We have compared their effectiveness against that of Fmoc-Asp(OtBu)-OH and Fmoc-Asp(OMpe)-OH in the well-established scorpion toxin II model peptide variants H-Val-Lys-Asp-Asn/Arg-Tyr-Ile-OH by treatments of the peptidyl resins with the Fmoc removal reagents containing piperidine and DBU at both room and elevated temperatures. The new derivatives proved to be extremely effective in minimising aspartimide by-products in each application.
authors.affiliation: Merck & Cie, Im Laternenacker 5, 8200, Schaffhausen, Switzerland.
authors.forename: Raymond
authors.initials: R
authors.lastname: Behrendt
authors.affiliation: Merck & Cie, Im Laternenacker 5, 8200, Schaffhausen, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Huber
authors.affiliation: School of Engineering and Architecture, Bd de Pérolles 80, 1705, Fribourg, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Martí
authors.affiliation: Merck Chemicals Ltd., Padge Road, Beeston, NG9 2JR, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: White
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D005449:Fluorenes; D010455:Peptides; D001224:Aspartic Acid; C075871:aspartimide
keywords: Fmoc SPPS; aspartic acid β-trialkylmethyl ester; aspartimide formation; protecting groups; racemisation