A Thiolactone Strategy for Straightforward Synthesis of Disulfide-Linked Side-Chain-to-Tail Cyclic Peptides Featuring an N-Terminal Modification Handle
| Autor: | Eirini Antonatou, Evelien Focquet, Dorien Van Lysebetten, Lieselot L. G. Carrette, Filip Du Prez, Stefania Felissati, Pieter Espeel, Annemieke Madder |
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| Rok vydání: | 2017 |
| Předmět: |
chemistry.chemical_classification
Molecular Structure 010405 organic chemistry Organic Chemistry Peptide 010402 general chemistry Native chemical ligation 01 natural sciences Biochemistry Combinatorial chemistry Peptides Cyclic Cyclic peptide 0104 chemical sciences chemistry.chemical_compound Lactones chemistry Click chemistry Thiolactone Side chain Molecular Medicine Amine gas treating Sulfhydryl Compounds Bifunctional Molecular Biology |
| Zdroj: | Chembiochem : a European journal of chemical biology. 19(6) |
| ISSN: | 1439-7633 |
| Popis: | The development of straightforward and versatile peptide cyclisation methods is highly desired to meet the demand for more stable peptide-based drugs. Herein, a new method for the synthesis of side-chain-to-tail cyclic peptides with the simultaneous introduction of an N-terminal handle, based on the introduction of an N-terminal thiolactone building block, is described. A primary amine liberates a homocysteine analogue from the thiolactone building block, which further enables cyclisation of the peptide through disulfide-bond formation with a C-terminal cysteamine. Postcyclisation modification can be achieved by using small bifunctional amines. Alternatively, the synthesis of lipopeptides is demonstrated through direct thiolactone opening with long-chain alkyl amines. |
| Databáze: | OpenAIRE |
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