Antibiotics 1 - Cell wall and Beta Lactams Flashcards Preview

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Flashcards in Antibiotics 1 - Cell wall and Beta Lactams Deck (70)
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1

Main barrier keeping drugs out of cell in gram positive

Bacterial membrane

2

Gram positives excrete...

B lactamase through the cell wall into the external environment

3

Outer membrane barrier property in gram negative?

excludes drugs, but some may stil get in through porins in the OUTER cell membrane

4

In gram negatives, where is the beta lactamase located?

in the periplasmic space

5

type with thicker PG

gram positive

6

Gram negatives have an ____ that contains ____ which may facilitate entry

outer membrane

porins

7

G- Peptidoglycan contains _______

meso-diaminopimelic acid residue

(DAP)

8

G+ peptidoglycan contains ____ instead of the ____ that gram negative contains

L-Lysine

DAP

9

Crosslinking occurs in G- between the ___ and ____

DAP and D-ala

10

G+ crosslinking occurs between...

L-Lys and terminal D-ala

11

S. aureus crosslink composition

5 glycine residues

12

Transpeptidase mechanism:

The OH from ___ attacks the ___ carbon of peptide-d-ala-d-ala

OH from Transpeptidase attacks the amide carbon

13

Transpeptidase mechanism: ____ is formed as an intermediate which is more reactive

Ester linkage

14

After the ester linkage is broken, a ____ intermediate is formed. 

tetrahedral

15

Final products of transpeptidase mechanism

Peptide- D-Ala-Gly-Gly -Peptide

+

Transpeptidase

16

B-lactam MOA

acylates the transpeptidase's serine residue in the enzyme active site.

 

--> inactivates the enzymes and inhibits cross linking.

17

reactivity of B lactam system is due to...

highly strained 4-membered ring

18

NCC bind of the B lactam is compressed to ___ from _____

compressed to 90 from normal 120 angle

19

Bond angle of a tetrahedral carbon

109

20

Stress can be releived in beta lactam strain by conversion of...

carbonyl to the tetrahydral intermediate

21

The beta lactal carbonyl is more reactive because...

its more like a ketone carbonyl than an amide carbonyl, because of the steric inhibition of overlap of the non-bonded electrons of the nitrogen with the adjacent carbonyl.

22

Penicillins assume a _____ structure with _____

folded ring structure with an sp3 hybridized nitrogen

23

There are many ____ which explains the heterogenecity of bacterial responses

penicillin binding proteins

24

The bacterial transpeptidases do not catalyze rxns with host cell proteins because...

the bacterial substrate contains unnatural D-ala residues that arent found in host cell proteins

25

Four mechanisms of resistance to beta-lactam

decreased cellular uptake

mutation of the PBPs

Presence of efflux pump

**Induction/elaboration of B-lactamases**

26

Four steps in B lactamase mechanism

[B lactamase + Penicillin] -->

Tetrahedral intermediate -->

Acylated B lactamase -->

[Regenerated enzyme + hydrolyzed penicillin]

27

Fast step in beta lactamase mechanism =

Hydrolysis of the acylated B-lactamase intermediate

28

__% of population has beta-lactam AB's

6-8%

29

How are beta lactams allergenic?

Drug acts as hapten - acylates host cell proteins

 

(generates covalent products that are "foreign")

30

Why can't the allergic reaction of beta lactam be overcome via structural manipulation of the compound?

the reaction originates from the pharmacore of the drug