FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1567162500> ?p ?o ?g. }

• W1567162500 abstract "Cyclic peptides are an important class of compounds with broad biological activities. Both natural as well as synthetic cyclic peptides have been recognized as a great resource and inspiration for drug discovery. Macrocyclization is recognized as an efficient way to restrict the conformational freedom of a peptide which often leads to increased affinity and selectivity. However, only a limited number of approaches for efficient peptide macrocyclization are presently available. Vancomycin is the most representative member of a family of glycopeptide antibiotics, which are the most important class of drugs for the treatment of resistant bacterial infections. The ongoing development of novel synthetic methodology to access conformationally restricted cyclic peptides encouraged us to develop effective approaches to mimic the bioactive conformation of vancomycin as closely as possible. This thesis describes the application of CuAAC and RuAAC macrocyclization for the synthesis of vancomycin mimics. The synthesis of cyclic 1,4-triazole-bridged tripeptides as vancomycin DE-ring mimics was described. Based on the successful synthesis of a series of linear tripeptides functionalized with alkyne and azide groups, the macrocyclization using CuAAC chemistry was successfully achieved. With the TBTA-promoted CuAAC macrocyclization strategy, two cyclic monomeric tripeptides, derived from ornithine and lysine, were successfully synthesized. As a relevant follow-up study after the successful application of CuAAC for the synthesis of the vancomycin DE-ring mimics, a RuAAC click-type macrocyclization protocol described, and a series of cyclic 1,5-triazole-bridged tripeptides as vancomycin DE-ring mimics was synthesized in good yield. The most constrained cyclic tripeptide obtained had only 13 atoms in the macrocyclic ring, while the lysine-derived tripeptide was of the same size as the vancomycin DE-ring containing 16 atoms. The RuAAC macrocyclization proved to be effective for the synthesis of 1,5-disubstituted triazole-containing cyclic tripeptides, and was superior compared to the CuAAC-based click cyclization with respect to the prevalent synthesis of monomeric cyclic peptides. With the successful application of the RuAAC macrocyclization for the synthesis of the DE-ring mimics of vancomycin, the synthesis of 1,5-triazole-bridged bicyclic vancomycin CDE-ring peptidomimetic using RuAAC macrocyclization was successfully achieved. The synthesis of a linear hexapeptide functionalized with alkyne and azide groups was carefully optimized and the synthesis could be accomplished within 10 steps with good to excellent yield. The RuAAC macrocyclization was successfully developed to synthesize the 1,5-triazole-bridged bicyclic peptidomimetic. The antibacterial activity of the synthesized bicyclic compound was investigated, but no obvious inhibition of the bacterial growth was observed. In general, the investigation as described in this thesis showed the successful application of CuAAC and RuAAC macrocyclization strategy for the synthesis of vancomycin DE- and CDE-ring mimics. Especially, the RuAAC chemistry turned out to be a very efficient strategy for the synthesis of small cyclic peptides with excellent intramolecular selectivity. Although the synthesized peptidomimetics were not biologically active, the methodology developed here could be applied for the structural optimization of cyclic peptides that lead to biologically interesting targets." @default.
• W1567162500 created "2016-06-24" @default.
• W1567162500 creator A5089860579 @default.
• W1567162500 date "2012-11-26" @default.
• W1567162500 modified "2023-09-27" @default.
• W1567162500 title "Synthesis of Triazole Bridged Vancomycin Mimics" @default.
• W1567162500 hasPublicationYear "2012" @default.
• W1567162500 type Work @default.
• W1567162500 sameAs 1567162500 @default.
• W1567162500 citedByCount "0" @default.
• W1567162500 crossrefType "dissertation" @default.
• W1567162500 hasAuthorship W1567162500A5089860579 @default.
• W1567162500 hasConcept C124790011 @default.
• W1567162500 hasConcept C137610392 @default.
• W1567162500 hasConcept C167392928 @default.
• W1567162500 hasConcept C178790620 @default.
• W1567162500 hasConcept C185592680 @default.
• W1567162500 hasConcept C21951064 @default.
• W1567162500 hasConcept C2777907353 @default.
• W1567162500 hasConcept C2779281246 @default.
• W1567162500 hasConcept C501593827 @default.
• W1567162500 hasConcept C55493867 @default.
• W1567162500 hasConcept C60984968 @default.
• W1567162500 hasConcept C69610077 @default.
• W1567162500 hasConcept C71240020 @default.
• W1567162500 hasConceptScore W1567162500C124790011 @default.
• W1567162500 hasConceptScore W1567162500C137610392 @default.
• W1567162500 hasConceptScore W1567162500C167392928 @default.
• W1567162500 hasConceptScore W1567162500C178790620 @default.
• W1567162500 hasConceptScore W1567162500C185592680 @default.
• W1567162500 hasConceptScore W1567162500C21951064 @default.
• W1567162500 hasConceptScore W1567162500C2777907353 @default.
• W1567162500 hasConceptScore W1567162500C2779281246 @default.
• W1567162500 hasConceptScore W1567162500C501593827 @default.
• W1567162500 hasConceptScore W1567162500C55493867 @default.
• W1567162500 hasConceptScore W1567162500C60984968 @default.
• W1567162500 hasConceptScore W1567162500C69610077 @default.
• W1567162500 hasConceptScore W1567162500C71240020 @default.
• W1567162500 hasLocation W15671625001 @default.
• W1567162500 hasOpenAccess W1567162500 @default.
• W1567162500 hasPrimaryLocation W15671625001 @default.
• W1567162500 hasRelatedWork W1930319253 @default.
• W1567162500 hasRelatedWork W1992362863 @default.
• W1567162500 hasRelatedWork W2003062728 @default.
• W1567162500 hasRelatedWork W2014097945 @default.
• W1567162500 hasRelatedWork W2142251662 @default.
• W1567162500 hasRelatedWork W2161779343 @default.
• W1567162500 hasRelatedWork W2293357505 @default.
• W1567162500 hasRelatedWork W2317683350 @default.
• W1567162500 hasRelatedWork W2326858137 @default.
• W1567162500 hasRelatedWork W2466138529 @default.
• W1567162500 hasRelatedWork W2481102436 @default.
• W1567162500 hasRelatedWork W2591505829 @default.
• W1567162500 hasRelatedWork W2906564933 @default.
• W1567162500 hasRelatedWork W2925024077 @default.
• W1567162500 hasRelatedWork W3010585844 @default.
• W1567162500 hasRelatedWork W3048739585 @default.
• W1567162500 hasRelatedWork W3201710598 @default.
• W1567162500 hasRelatedWork W60463505 @default.
• W1567162500 hasRelatedWork W91979755 @default.
• W1567162500 hasRelatedWork W2095331207 @default.
• W1567162500 isParatext "false" @default.
• W1567162500 isRetracted "false" @default.
• W1567162500 magId "1567162500" @default.
• W1567162500 workType "dissertation" @default.