RESUMO
Via a Mannich reaction involving a dibenzyliminium species and the titanium enolates of Evans' chiral acylated oxazolidinones the ß(2)-amino acids (R)- and (S)-Fmoc-ß(2)homovaline and (R)-Fmoc-ß(2)homoleucine are synthesized. These building blocks were used, in combination with commercially available α- and ß(3)-amino acids, for the synthesis of the cyclo-(αß(3)αß(2)α)(2) peptide 2 and the cyclo-(αß(2)αß(3)α)(2) peptides 3-5. The peptides 2-5 were screened for their ability to inhibit a small panel of Gram-negative and Gram-positive bacterial strains.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Gramicidina/química , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Aminoácidos/síntese química , Aminoácidos/química , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Humanos , Peptídeos Cíclicos/químicaRESUMO
The grafting-to of a peptide to a side chain functional polymer was investigated using "click" chemistry. Two click reactions were compared: the copper-free strain-promoted azide-alkyne 1,3-cycloaddition (SPAAC) and the traditional copper-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). For the resulting comb-shaped products, it was found that the steric bulk of the conjugation moiety used in SPAAC limits the degree of grafting for these highly dense systems, whereas CuAAC gives (near) quantitative functionalization.
Assuntos
Química Click/métodos , Gramicidina/química , Metacrilatos/química , Ácidos Polimetacrílicos/química , Alcinos/química , Azidas/química , Catálise , Cobre/química , Reação de Cicloadição , Estrutura Molecular , Triazóis/químicaRESUMO
The synthesis of new analogues of the cationic antimicrobial peptide gramicidin S, having a modified D-phenylalanine residue, their antibacterial properties against several gram positive and negative strains, as well as their hemolytic activity is reported.
Assuntos
Antibacterianos/síntese química , Gramicidina/análogos & derivados , Fenilalanina/química , Antibacterianos/química , Antibacterianos/farmacologia , Eritrócitos/efeitos dos fármacos , Gramicidina/síntese química , Gramicidina/farmacologia , Hemólise , Humanos , Testes de Sensibilidade MicrobianaRESUMO
The influence of replacing the d-phenylalanine residue with substituted and unsubstituted azoles on the structure and biological activity of the antibiotic gramicidin S was investigated against a representative panel of Gram-positive and Gram-negative bacteria strains. Substituted triazole derivatives, obtained using a convergent synthetic strategy, are as active as gramicidin S, provided that any substituent on the triazole moiety is not too large. The unsubstituted triazole derivative was biologically less active than the parent natural product, gramicidin S. In general for the triazole series, the hemolytic activity could be correlated with the antibacterial activity, that is, the higher the antibacterial activity, the higher the toxicity towards blood cells. Interestingly, its imidazole counterpart showed high antibacterial activity, combined with significantly diminished hemolytic activity.