RESUMO
A systematically designed and synthesized ribitol phosphate (RboP) oligomer using a series of building blocks, which make up the wall teichoic acid (WTA) of S. aureus, is presented. Based on the use of a solution-phase phosphodiester synthesis, a library of ribitol phosphate tetramers, decorated with d-alanine and N-acetylglucosamine (GlcNAc), were generated. The synthesized RboP tetramers showed increased cytokine levels in mice in a subcutaneous air pouch model.
Assuntos
Oligossacarídeos/síntese química , Organofosfatos/síntese química , Ribitol/análogos & derivados , Ribitol/síntese química , Staphylococcus aureus/química , Ácidos Teicoicos/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Parede Celular/química , Glicerol/química , Humanos , Interleucina-6/metabolismo , Lactonas/química , Camundongos Endogâmicos BALB C , Estrutura Molecular , Organofosfatos/química , Ribitol/química , Bibliotecas de Moléculas Pequenas/síntese químicaRESUMO
Herein we correlate secondary structure perturbation with changes in the solid-state molecular architectures of an elongated hexagonal plate-shaped foldecture derived from the self-assembly of rigid 12-helical ß-peptide foldamers to which a flexible C-terminus α-leucine moiety has been appended. This study provides the first complete characterization of the directional molecular packing patterns of individual foldamer components within a foldecture, from which a 3D molecular-level picture of the entire foldecture was unambiguously constructed.
RESUMO
Our previous study showed that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh(8)Gua) glycosylase 1 (OGG1) activity and that its viability is severely affected by 8-hydroxydeoxyguanosine (8-oxodeoxyguanosine; oh(8)dG). In the present study, the nature of the killing action of oh(8)dG on KG-1 was investigated. Signs observed in oh(8)dG-treated KG-1 cells indicated that death was due to apoptosis, as demonstrated by: increased sub-G(1) hypodiploid (apoptotic) cells, DNA fragmentation, and apoptotic body formation; loss of mitochondrial transmembrane potential, the release of cytochrome c from mitochondria into the cytosol, and the down-regulation of bcl-2; and the activation of caspases 8, 9, and 3, and the efficient inhibition of the apoptotic process by caspases inhibitors. This apoptosis appears not to be associated with Fas/Fas ligand because the expressions of these proteins were unchanged. Apoptotic KG-1 cells showed a high concentration of oh(8)Gua in DNA. Moreover, the increased concentration of oh(8)Gua in DNA, and the apoptotic process were not suppressed by the antioxidant, N-acetylcysteine, and thus the process is independent of reactive oxygen species. Of the 18 cancer cell lines treated with oh(8)dG, 3 cell lines (H9, CEM-CM3, and Molt-4) were found to be committed to apoptosis, and all of these showed very low OGG1 activity and a marked increase in the concentration of oh(8)Gua in DNA. These observations indicate that in addition to its mutagenic action, oh(8)Gua in DNA disturbs cell viability by inducing apoptosis.
