Chemistry of antibiotics Flashcards
Beta lactam ring
Mimics d-ala-d-ala dipeptide in crosslinking
Ring is highly strained making it electrophilic
Forms a stable acyl-enzyme complex and removes nucleophile. This is irreversible inhibtion
High conc of antibiotic leads to less lysis called the ‘eagle phenomenon’
3 forms of resistance against b-lactams
Target modification- results in MRSA
Amidases- removes penicillin side chain
Beta lactamases
Beta-lactamase
Uses serine/cysteine residue to form acyl-enzyme complex which inactivates the drug
Evolved from PBP’s and B-lactamases are TEM 1 and 2
4 classes of b-lactamase
A-penicillinase (TEM 1/2)
B-metallo b lactamase
C-cephalosporins
D- extended spectrum b lactamases
New antibiotic discovery
Natural product screening
Manipulate biosynthetic pathways to make semisynthetic antibiotics-change penicillin branching
Engineering biosynthetic pathways using genetic techniques
6-aminopenicillanic acid used to make semi synthetic
Cephalosporins
Binds to pbp’s
Used when there is resistance to penicillin and made from penicillin n
Cephalexin preferred due to almost complete absorption despite lower antibacterial activity
Most cephalosproins given orally are cephalexin derivatives
overcoming b lactamase
modify drug
coadmin blocking antibiotic
suicide inhibitor- becomes a reactive species that inactivates b lactamase
Examples of irreversible b lactamase inhibitors
Sulbactam
6 b bromopenicillin
thienamycin
clavulanic acid (with amoxacillin it is co amoxiclav) does not work on class b,c,d
Not effective in vitro due to difficulty crossing biological membranes