RESUMO
A new category of phosphonium based cationic amphiphilic peptides has been developed and evaluated as potential antimicrobial peptides and cell penetrating peptides. The required building blocks were conveniently accessible from cysteine and could be applied in a solid phase peptide synthesis protocol for incorporation into peptide sequences. Evaluation of the antimicrobial properties and cellular toxicity of these phosphonium based peptides showed that these "soft" cationic side-chain containing peptides have poor antimicrobial properties and most of them were virtually non toxic (on HEK cells tested at 256 and 512 µM) and non-haemolytic (on horse erythrocytes tested at 512 µM), hinting at an interesting potential application as cell penetrating peptides. This possibility was evaluated using fluorescent peptide derivatives and showed that these phosphonium based peptide derivatives were capable of entering HEK cells and depending on the sequence confined to specific cellular areas.
RESUMO
Contrary to other studies, here we describe cysteine (Cys) pseudoproline-containing peptides with short deprotection times in TFA. The deprotection times fell in the same range as other protecting groups commonly used in SPPS (e.g., 1-3 h). Moreover, when using Cys pseudoprolines as peptide macrocyclization-enhancing moieties a considerable reduction in reaction time was observed compared to a peptide containing trityl protected Cys.
Assuntos
Cisteína/análogos & derivados , Cisteína/química , Dipeptídeos/química , Prolina/análogos & derivados , Compostos de Sulfidrila/química , Tiazóis/química , Ciclização , Estrutura Molecular , Prolina/química , Técnicas de Síntese em Fase SólidaRESUMO
A novel immobilized N-chlorosuccinimide resin was developed for peptide disulfide bond formation in combinatorial libraries. The resin is prepared in a simple two-step process from commercial starting materials. Disulfide formation is initiated by adding a peptide solution to the resin, and excess reagent is removed by a convenient filtration upon completion of disulfide formation. Completion of disulfide formation is rapid and clean, as demonstrated by the oxidation of a small nonapeptide library. This immobilized reagent allows a wider scope for the use of N-chlorosuccinimide-based disulfide formation in combinatorial chemistry.
Assuntos
Dissulfetos/síntese química , Peptídeos/química , Resinas Sintéticas/química , Succinimidas/química , Dissulfetos/química , Estrutura Molecular , Resinas Sintéticas/síntese química , Succinimidas/síntese químicaRESUMO
N-Chlorosuccinimide is described as a widely applicable on-resin disulfide-forming reagent. Disulfide bond formation was completed within 15 min in DMF. This strategy was successfully used in the synthesis of oxytocin and a regioselective synthesis of an α-conotoxin. Moreover, disulfide formation with N-chlorosuccinimide was found to be compatible with oxidation-prone methionine and tryptophan.
Assuntos
Dissulfetos/química , Succinimidas/química , Conotoxinas/síntese química , Indicadores e Reagentes , Metionina/química , Estrutura Molecular , Oxirredução , Polímeros/química , Técnicas de Síntese em Fase Sólida , Triptofano/químicaRESUMO
Trimethoxyphenylthio (S-Tmp) is described as a novel cysteine protecting group in Fmoc solid phase peptide synthesis replacing the difficult to remove tert-butylthio. S-Tmp and dimethoxyphenylthio (S-Dmp) were successfully used for cysteine protection in a variety of peptides. Moreover, both groups can be removed in 5 min with mild reducing agents. S-Tmp is recommended for cysteine protection, as it yields crude peptides of high purity.