Towards new antibiotics targeting bacterial transglycosylase: Synthesis of a Lipid II analog as stable transition-state mimic inhibitor.

Described here is the asymmetric synthesis of iminosugar 2b, a Lipid II analog, designed to mimic the transition state of transglycosylation catalyzed by the bacterial transglycosylase. The high density of functional groups, together with a rich stereochemistry, represents an extraordinary challenge for chemical synthesis. The key 2,6-anti- stereochemistry of the iminosugar ring was established through an iridium-catalyzed asymmetric allylic amination.

Structure-based design of bacterial transglycosylase inhibitors incorporating biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties.

Transglycosylase (TGase) is essential to biosynthesis of peptidoglycan for formation of bacterial cell wall. Moenomycin is a potent TGase inhibitor, but not used in clinic treatment due to its poor pharmacokinetics. The E-F disaccharide, phosphoglycerate and lipid tail in moenomycin are crucial elements for TGase inhibition and antibacterial activity.

Affinity-Based Screen for Inhibitors of Bacterial Transglycosylase.

The rise of antibiotic resistance has created a mounting crisis across the globe and an unmet medical need for new antibiotics. As part of our efforts to develop new antibiotics to target the uncharted surface bacterial transglycosylase, we report an affinity-based ligand screen method using penicillin-binding proteins immobilized on beads to selectively isolate the binders from complex natural products. In combination with mass spectrometry and assays with moenomycin A and salicylanilide analogues (1-10) as reference inhibitors, we isolated four potent antibacterials confirmed to be benastatin derivatives (11-13) and albofungin (14).

Effectiveness of 10-year vaccination (2001-2010) on Hepatitis A in Tianjin, China.

Vaccination is an effective strategy to prevent and control the transmission of hepatitis A. Hepatitis A immunization program has been taken into effect since 2001 in Tianjin, China. This study evaluated the effectiveness of strategies in the prevention and control of hepatitis A.

[Current status of hepatitis B immunization and strengthened immune memory among first-year middle school students in Tianjin].

Objective: To investigate the immunization status of hepatitis B vaccine who were inoculated at birth, HBV infections and the vaccine booster effect in the first-year middle school students (12 - 14 years old).

Methods: A cluster, stratified simplified random sampling method was administrated. The sample size was at least 218, which was calculated by Epi Info 3.

[Study on the report criteria and focus management mode of the virus hepatitis cases in Tianjin].

Objective: To establish the focus management mode and the report criteria more perfectly for the virus hepatitis cases, especially for the hepatitis B.

Methods: One district was set as the research area, in which there was enough cases resource and relatively separated from the other districts, then a first or second-class hospital was appointed to take the cases focus diagnosis, report and management.

Results: The focus hospitals had reported 97% (323/331) of cases in the research area between June,2007 and June,2008; moreover,the rate in establishing case-card was 97.