Penicillin binding

Table 10. Penicillin Binding Proteins (PBPs) of E. coll...

Molecular mechanisms of penicillins binding with biopolymers and membranes 98ZOR655. 

Aziridinium ion-based click chemistry provides convenient access to pyrazolo[l,2-ajpyrazoles, active inhibitors of penicillin-binding proteins [58, 59]. Ring-opening of aziridinium ions 32 at the benzylic position with hydrazine, followed by intramolecular cyclization, gave pyrazolidin-3-ones 37 in excellent yields (Scheme 12.27). Heating of the hydrazides 37 with aromatic aldehydes at reflux in absolute... 

An example for proteases are the (3-lactamases that hydrolyse a peptide bond in the essential (3-lactam ring of penicillins, cephalosporins, carbapenems and monobac-tams and, thereby, iireversibly inactivate the diug. 13-lactamases share this mechanism with the penicillin binding proteins (PBPs), which are essential enzymes catalyzing the biosynthesis of the bacterial cell wall. In contrast to the PBPs which irreversibly bind (3-lactams to the active site serine, the analogous complex of the diug with (3-lactamases is rapidly hydrolyzed regenerating the enzyme for inactivation of additional (3-lactam molecules. 

In contrast to macrolides, the targets of (3-lactams, the penicillin binding proteins (PBPs) require several mutations in order to become resistant while simultaneously maintaining their viable function as cell wall transpeptidases/transglycosidases. Thus, in order to achieve clinically relevant resistance Streptococcus pneumoniae uses a unique strategy to rapidly accumulate several point mutations. Due to its natural competence for transformation during respiratory tract... 

Staphylococcus aureus cells can acquire large DNA fragments containing the mecA gene which encodes a complete new penicillin binding protein 2A (PBP 2A), as part of a transposon. PBP2A can substitute the natural set of penicillin-sensitive PBPs thereby mediating a complete cross resistance to all (3-lactam antibiotics. 

Lepage S et al (1997) Dual multimodular class A penicillin-binding proteins in Mycobacterium leprae. J Bacteriol 179 4627 1630... 

The enterococcal penicillin-binding-protein PBP5 binds penicillin with low affinity. The overproduction of this PBP is able to compensate the loss of the others which are inhibited by the drug. 

SxxK Free-standing Penicillin-binding Protein... 

SxxK free-standing penicillin-binding proteins (PBPs) are uncoupled SxxK acyl transferases that work mainly as bacterial wall peptidoglycan-hydrolases and function as auxiliary cell-cycle proteins. They are not essential. 

Penicillin Binding Protein Pentasaccharide Peptide Mass Fingerprint Peptide YY Peptidoglycans Peptidyl Transferase Center Peptidyl-Dipeptidase PERI... 

Enzymatic trapping Some -lactam antibiotics Penicillin-binding proteins... 

Depends on chemical nature of drug and on type of organism, t Penicillin-binding proteins. 

Georgopapadakou N.H. (1993) Penicillin-binding proteins and bacterial resistance to /Mactams. 

Alteration of the penicillin-binding proteins (PBPs) inactivating P-lactams... 

Mode of action Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls bacteria usually lyse from ongoing autolytic enzyme activity... 

Xanthine oxidase Thrombin Cyclooxygenases Penicillin binding proteins Angiotensin converting enzyme... 

Further activities in research into 6-amino-7-oxotetrahydro-177,577-pyrazolo[l,2- ]pyrazole-l-carboxylic acid derivatives 677 exhibiting inhibition of penicillin-binding protein have been reported <1997JHC1323>. 

NB2001 (23), a prodrug of triclosan, has been developed based on the enzyme-catalyzed therapeutic activation (ECTA) concept. Evidence supporting ring opening of the cephalosporin moiety by penicillin-binding proteins and/ or (3-lactamases to release triclosan at the bacterium site, as well as sub-pg/mL MIC on [3-lactamase-positive strains, demonstrates the potential of this approach [42]. 

Lactam antibiotics, such as cephalosporins, and penicillins, such as ampicillin (11) and aztreonam, covalently modify their protein targets. Alkyne-functionalized versions of these antibiotics, for example, AmpN (12), were used to probe various penicillin-binding proteins in vitro and in vivo using CC-ABPP [36,37],... 

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