Hydrazine hydrate: A new reagent for Fmoc group removal in solid phase peptide synthesis |
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Authors: | Verónica Rodríguez Julieth T Román Ricardo Fierro Zuly J Rivera Javier E García |
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Institution: | 1. Chemistry Department, Universidad Nacional de Colombia, Bogotá Carrera 45 No 26-85, Building 451, Office 334, Bogotá Zip Code 11321, Colombia;2. Pharmacy Department, Universidad Nacional de Colombia, Bogotá Carrera 45 No 26-85, Building 450, Office 203, Bogotá Zip Code 11321, Colombia |
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Abstract: | In solid-phase peptide synthesis using the Fmoc/tBu strategy (SPPS-Fmoc/tBu), an orthogonal protection scheme of amino acids is used; specifically, the alpha-amine group is protected by the 9-fluorenylmethyloxycarbonyl (Fmoc) group, which is removed by weak bases, while side chains are protected by groups that are acid labile. We demonstrated that hydrazine hydrate is an efficient reagent for eliminating the Fmoc group in SPPS-Fmoc/tBu. First, experimental conditions were established for Fmoc group removal from Fmoc-Val-OH in solution. It was determined that the Fmoc group was completely removed with 16% hydrazine hydrate in DMF after 60?min at rt. Second, SPPS-Fmoc/tBu using hydrazine hydrate for Fmoc group removal was standardized. The Fmoc group removal was completed using 16% hydrazine hydrate in DMF for 10?min at rt (twice). When the reaction of Fmoc group removal was microwave-assisted, the reaction only required 30?s to efficiently remove the Fmoc group in SPPS-Fmoc/tBu. The method reported here can be routinely used, and it is equivalent to conventional SPPS-Fmoc/tBu methodologies where 4-methylpiperidine or piperidine is used. |
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Keywords: | Hydrazine hydrate Fmoc group removal Solid phase peptide synthesis Orthogonal protection 4-Methylpiperidine |
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