Aiming at the direct preparation of peptide thioesters by an Fmoc solid-phase method, we searched a new deblocking reagent, which efficiently removed Fmoc groups while keeping the thioester intact. The deblocking reagent, which contains 1-methylpyrrolidine, hexamethyleneimine and HOBt in a one to on
An improved deblocking agent for direct Fmoc solid-phase synthesis of peptide thioesters
β Scribed by Xianzhang Bu; Guiyang Xie; Chi Wang Law; Zhihong Guo
- Publisher
- Elsevier Science
- Year
- 2002
- Tongue
- French
- Weight
- 133 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0040-4039
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β¦ Synopsis
To synthesize peptide thioesters directly on a solid support for use as substrate analogues for thioesterases in non-ribosomal peptide synthases, we modified a reagent compatible with Fmoc solid-phase peptide synthesis that efficiently removes the protecting group while keeping the thioester intact. The deprotecting reagent, consisting of DBU and HOBt, was successfully used to prepare a decapeptide in high yield.
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The acid-mediated cleavage of a synthetic thioxo peptide was monitored using deprotection cocktails with varying concentrations of TFA. Thioxo peptides are acid labile, undergoing cleavage at the amide linkage immediately following the thioamide linkage in the sequence. This acid lability makes Fmoc
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