The aspartimide problem in Fmoc-based SPPS. Part II. |
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Authors: | M Mergler F Dick B Sax C Sthelin T Vorherr |
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Institution: | BACHEM AG, Hauptstr. 144, CH-4416 Bubendorf, Switzerland. |
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Abstract: | The sequence dependence of base-catalysed aspartmide formation during Fmoc-based SPPS was systematically studied employing the peptide models H-Val-Lys-Asp-Xaa-Tyr-Ile-OH. The extent of formation of aspartimide and related by-products was determined by RP-HPLC. Considerable amounts of by-products were formed in the case of Xaa = Asp(OtBu), Arg(Pbf), Asn(Mtt), Cys(Acm) and unprotected Thr. Aspartimide formation could be diminished by incorporation of Asp(OMpe) or by employing milder methods for Fmoc cleavage, e.g. hexamethyleneimine/N-methylpyrrolidine/HOBt/NMP/DMSO 4:50:4:71:71 (v/v/w/v/v). |
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Keywords: | aspartimide formation backbone protection Fmoc‐solid phase peptide synthesis Fmoc cleavage Asp(OMpe) |
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