Antibiotic chemistry Flashcards

1
Q

difference between gram negative and positive bacterial cell wall?

A

gram positive has a thicker layer of peptidoglycan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

structure of peptidoglycan?

A
  • alternating segments of NAG and NAM cross-linked by tetrapeptide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how does activity of R group of Beta lactams change with EWG or bulky substituents?

A

EWG - N becomes less nucleophilic
bulky - steric hinderance to beta-lactamase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what can the beta lactam ring be opened by?

A

OH, NH2, SH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how does the carboxylic acid of beta lactams interact with enzyme?

A

negatively charged and forms salt bridge in enzyme pocket

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

enzymes involved in bacterial cell wall synthesis?

A

penicillin binding proteins PBP or DD-transpeptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

mechanism of action of PBPs?

A

1) cleavage of D-alanyl D-alanine bond of peptide unit precursor
2) acyl-enzyme intermediate formed
3) breakdown of intermediate to form new peptide bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what do beta lactams resemble?

A

tetrapeptide chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how do beta lactams work?

A
  • PBP bind to antibiotic instead of tetrapeptide
  • PBP becomes disabled, cross linking of peptidoglycan fails
  • weakens cell wall
  • bacteria attempt to divide and cell wall collapses, killing bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how has resistance to beta-lactams come about?

A

bacteria evolved an enzyme (Beta-lactamases/penicillinases) that break the ring so antibiotics become ineffective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

2 solutions to combat resistance?

A

enzyme inhibitors - inactivate enzymes
newer antibiotics - larger side chains to not fit enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what makes penicillins unstable in acid?

A

amide side chain acts as an internal nucleophile which opens up the beta-lactam ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what makes penicillin V a weaker internal nucleophile?

A

add oxygen/ ether bond so O accepts electron density from C=O

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how do bactoprenol inhibitors such as bacitracin work?

A

block bactoprenol phosphate transporter so that new peptidoglycan cant be made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

role of bactoprenol phosphate transporter?

A

lets NAM and NAG cross membrane to synthesise new peptidoglycan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what routes should bacitracin never be given by and why?

A

IV or IM as its highly nephrotoxic
- used topically for systemic infections

17
Q

how do beta-lactamase enzyme inhibitors work? (clavulanic acid, tazobactum)

A

permanently bind to enzyme to disable them so penicillins can work

18
Q

how do glycopeptide antibiotics work? (vancomycin)

A

inhibit cell wall synthesis by latching to tetrapeptide chain - prevents link to PBP enzyme

19
Q

how are glycopeptide antibiotics usually given?

A

not absorbed in GI tract so given IV typically