Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis
Yi Yang, Lena Hansen
Abstract
DKP (diketopiperazine) formation is a ubiquitous side reaction in SPPS (solid-phase peptide synthesis) that is highly sequence-dependent. Secondary amino acids are extremely prone to host such a side reaction. DKP formation is predominantly induced at the Fmoc (fluorenylmethyloxycarbonyl)-removal step mediated by a secondary amine, which conventionally employs piperidine/DMF (dimethylformamide). In this study, alternative Fmoc-removal solution 2% DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)/5% piperazine/NMP (N-methyl-2-pyrrolidone) led to drastic DKP reduction relative to 20% piperidine/DMF.
Topics & Concepts
PiperidineChemistrySolid-phase synthesisPiperazinePeptide synthesisAmine gas treatingPeptideCombinatorial chemistryDimethylformamideOrganic chemistryStereochemistryBiochemistrySolventChemical Synthesis and AnalysisPeptidase Inhibition and AnalysisAntimicrobial Peptides and Activities