Solid-phase synthesis of 5-arylhistidine-containing peptides: from linear antimicrobial peptides to cyclic peptides derived from arylomycins and aciculitins
The incorporation of unsymmetrical biaryl systems into peptide sequences is a strategy that can improve their biological activity. Due to the difficulty of arylating the 4(5}-position of the imidazole ring, this doctoral thesis was focused on the development of efficient methodologies for the solid-...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/380739 |
| Acceso en línea: | http://hdl.handle.net/10803/380739 |
| Access Level: | acceso abierto |
| Palabra clave: | Histidine Histidina Biaryl peptides Pèptids biarílics Péptidos biarílicos Microwave irradiation Irradiació de microones Irradiación de microondas Macroarylation Macroarilació Macroarilación Arylomycins Arilomicines Arilomicinas Suzuki-Miyaura reaction Reacción Suzuki-Miyaura Reacció Suzuki-Miyaura 547 |
| Sumario: | The incorporation of unsymmetrical biaryl systems into peptide sequences is a strategy that can improve their biological activity. Due to the difficulty of arylating the 4(5}-position of the imidazole ring, this doctoral thesis was focused on the development of efficient methodologies for the solid-phase synthesis of 5-arylhistidine-containing antimicrobial undecapeptides through a Suzuki-Miyaura reaction under microwave irradiation. The extension of this protocol allowed the preparation of biaryl cyclic peptides of different ring sizes bearing a His-Phe or His-Tyr biaryl linkage. Then, it was developed a procedure for the total solid-phase synthesis of biaryl cyclic lipopeptides derived from arylomycins. These strategies were extended to the preparation of biaryl cyclic analogues of the marine bicyclic pptides aciculitins. In particular, it was achieved the synthesis of analogues of the northern and the southern hemispheres of aciculitins as well as biaryl bicyclic peptides incorporating a Phe-Phe, a Phe-Tyr, a His-Tyr or a Tyr-Tyr biaryl bridge |
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