ABSTRACT
Teixobactin, a cyclic-peptide antibiotic, destroys the cell walls of Gram-positive bacteria. It is therefore difficult for bacteria such as meticillin-resistant Staphylococcus aureus to develop resistance to it. Many scholars have studied the structure-activity relationship (SAR) of teixobactin. After reviewing the reports related to the discovery, structure, total synthesis and SAR of teixobactin, we found that the total synthesis of teixobactin was very difficult. The N-terminal methyl modification, ester bond and allo-End were unnecessary for the activity, the configuration of amino acids at the positions 1, 4, 5 and 8 could greatly influence the antibacterial activity, and the substitution of the amino acids at the 3, 4, 9 and 10 positions by Lys could retain the antibacterial activity.
ABSTRACT
Protein-protein interactions(PPI)with large and shallow interfaces are generally undruggable targets. Many PPI in-volved in vital biological processes are mediated by helixes,therefore PPI can be easily targeted by helical epitope mimics. However, the application of peptide was limited by its conformational flexibility and low stability until the significant work was done by Arora ,et al who applied nucleation and crosslinking strategies to lock peptides in helical conformation. The conformation-locked strategies helps to improve peptide stability,cell permeability,and afterwards target intracellular PPI. At present,the conformation-locked strategies of peptides have achieved great development,and have become a hot spot in peptide research field. In this paper,the recent develop-ment,centering nucleation strategies,applications and bright prospects of helical conformation-locked peptides,are reviewed in order to provide theoretical basis for drug design based on PPI.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of nuclear factor kappa B (NF-kB), transforming growth factor beta1 (TGFbeta1), fibronectin (FN) in liver from diabetic rats.</p><p><b>METHODS</b>Twenty male Sprague-Dawley rats were divided randomly into two groups: normal control group (n = 10) and type 2 diabetic group (n = 10). After 4 weeks of high-fat feeding, diabetic group rats were injected with low dosage streptozotocin (30 mg/kg) intraperitoneally to induce type 2 diabetic rat models. The diabetic rats received high-fat feeding for another 12 weeks. At the end of the experiment, the fibrosis lesion was observed under light microscopy after Masson staining. The mRNA levels of NF-kB, TGFbeta1, FN from rats liver were assayed by semi-quantity RT-PCR, the protein levels of NF-kB, TGFbeta1, FN was detected by IHC.</p><p><b>RESULTS</b>Fibrosis was found in diabetic rats. The levels of TGFbeta1, FN mRNA in liver tissues increased in diabetic rats compared with normal control rats (0.91+/-0.19 vs 0.47+/-0.20, t = 5.233, P less than 0.05; 1.85+/-0.70 vs 1.22+/-0.39, t = 2.463, P less than 0.05). And the protein levels of NF-kB P65, TGFbeta1, FN in liver tissues from diabetic rats were significantly higher than those in normal control rats (10978.77+/-8782.59 vs 4206.86+/-1430.56, Z = 1.979, P less than 0.05; 8551.00+/-4768.68 vs 4036.85+/-1051.12, Z = 2.303, P less than 0.05; 16980.30+/-11529.29 vs 5701.95+/-9461.75, t = -2.391, P less than 0.05).</p><p><b>CONCLUSION</b>Upregulation of NF-kB, TGFbeta1, FN in liver tissues may play a role in the hepatic fibrogenesis in diabetic rats.</p>