666728-50-3

Upstream product

• 2771-48-4 methyl 2-acetamido-3,4,6-O-triacetyl-2-deoxy-β-D-glucopyranoside 
• 3946-01-8 methyl N-acetyl-β-D-glucosaminide 
• 10378-06-0 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoso)[1,2-d]-2-oxazoline 
• 87038-18-4 methyl 2-acetylamido-4,6-O-benzylidene-2-deoxy-β-D-glucopyranoside 
• 658-78-6 1-nitro-4-trifluoroacetoxy-benzene 
• 129172-14-1 methyl 2-acetamido-4,6-O-benzylidene-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside 

Downstream Products

• 666728-52-5 2-{2-[2-(7-acetylamino-6-methoxy-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yloxy)-propionylamino]-propionylamino}-4-{5-benzyloxycarbonylamino-1-[1-(1-benzyloxycarbonyl-ethylcarbamoyl)-ethylcarbamoyl]-pentylcarbamoyl}-butyric acid benzyl ester 

Relevant academic research and scientific papers

Activation for catalysis of penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus by bacterial cell wall

Methicillin-resistant Staphylococcus aureus (MRSA) has acquired a unique penicillin-binding protein (PBP), PBP 2a, which has rendered the organism resistant to the action of all available β-lactam antibiotics. The X-ray structure of PBP 2a shows the active site in a closed conformation, consistent with resistance to inhibition by β-lactam antibiotics. However, it is known that PBP 2a avidly cross-links the S. aureus cell wall, which is its physiological function. It is shown herein that synthetic fragments of the bacterial cell wall bind in a saturable manner to PBP 2a and cause a conformational change in the protein that makes the active site more accessible to binding to a β-lactam antibiotic. These observations and measurements point to a novel strategy by nature to keep the active site of PBP 2a sheltered from the inhibitory activity of the antibiotics, yet it becomes available to the polymeric cell wall by a requisite conformational change for the critical cell wall cross-linking reaction. Copyright

Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria

The major constituent of the bacterial cell wall, peptidoglycan, is comprised of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with an appended peptide. Penicillin-binding proteins (PBPs) are involved in the final stages of bacterial cell wall assembly. Two activities for PBPs are the cross-linking of the cell wall, carried out by DD-transpeptidases, and the DD-peptidase activity, that removes the terminal D-Ala residue from peptidoglycan. The DD-peptidase activity moderates the extent of the cell wall cross-linking. There exists a balance between the two activities that is critical for the well-being of bacterial cells. We have cloned and purified PBP5 of Escherichia coli. The membrane anchor of this protein was removed, and the enzyme was obtained as a soluble protein. Two fragments of the polymeric cell wall of Gram-negative bacteria (compounds 5 and 6) were synthesized. These molecules served as substrates for PBP5. The products of the reactions of PBP5 and compounds 5 and 6 were isolated and were shown to be D-Ala and the fragments of the substrates minus the terminal D-Ala. The kinetic parameters for these enzymic reactions were evaluated. PBP5 would appear to have the potential for turnover of as many as 1.4 million peptidoglycan strands within a single doubling time (i.e., generation) of E. coli.