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Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis.

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.

SUBMITTER: Yang Y

PROVIDER: S-EPMC9016848 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis.

Yang Yi Y Hansen Lena L

ACS omega 20220329 14

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% piper ...[more]

PMID: 35449974

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