Drug Action 2 - Cuong Tu

Discussions can be started now and questions can be asked whenever. This topic is pretty straightforward because it's Drug Action and just has to do with how drugs work with what atoms they have.

OBJECTIVE: D.8.3 Explain the importance of the beta-lactam ring action of penicillin

external image penicillin-core1.png

In 1929, Dr. Alexander Fleming isolated a chemical he called "Penicillin" from the fungus Penicillium notatum.

-He stated that Penicillin was able to inhibit the growth of bacteria and thus paved its pathway towards becoming grown, extracted, and purified into an effective drug (the first drug quality version was produced in 1940)

-Penicillin therefore became an antibiotic and was used to treat bacterial infections.

-Several different types of Penicillin exist; however, they all share the common trait of having the beta-lactam ring.

Structural Diagram of Penicillin-1

BETA-LACTAM RINGexternal image betalactam.jpg

-A Beta-Lactam is a four-membered ring with an amide nitrogen and a ketone group (3 carbons and a nitrogen atom)
-As you can see, it's not only used with penicillin but with several other antibiotics
-Within the picture, the beta-lactam is visualized as the "square" with then nitrogen and double bonded oxygen, which ultimately resembles a "ring"

Examples Diagrams of Antibiotics with the Beta-Lactam Ring-2


*Bacteria need their cell walls to retain their structure and prevent bursting by osmosis.
external image Peptoglycan.jpg
-Peptidoglycan is a polymer that is the most important part of the cell wall

-It contains N-acetyl muramic acid alternating with N-acetyl glucosamine, which are cross-linked by amino acids.

Diagram of the Petidoglycan polymer with the Petide Bridge being the cross-links necessary to complete the Cell Wall-3
The Beta-Lactam Ring inhibits bacterial cell wall synthesis by binding with both the transpeptidase and D-alanyl carboxypeptidase enzymes.

*Two major enzymes. transpeptidase and D-alanyl carboxypeptidase (AKA PENICILLIN BINDING PROTEINS) contribute to "cross-linking"... vital step in completing the cell wall.

Diagram of PBP Purpose-4
The Beta-Lactam Ring binds at the active site of the transpeptidase enzyme by mimicking the D-alanyl-D-alanine residues that would normally bind to this site (The pink objects are the Beta-Lactam Rings).

Diagram of Beta-Lactam Interference-5

This causes the cell wall to improperly form, causing the bacteria to become hypotonic, ultimately meaning that water would keep flowing into the cell until it explodes!

external image 3779-2-crestock%20balloon%20burst.jpg
Water Balloon Bursting-6

OBJECTIVE 2- D.8.4 Explain the increased potency of diamorphine (heroin) compared to morphine

Morphine vs Heroin

One of the most powerful analgesics, Morphine is used to block specific receptor sites on nerve cells, thereby preventing pain signals from reaching the brain and thus acts as a pain reliever.

external image morphine.gif
Structural Diagram of Morphine with hydroxyl groups that will be replaced to create Heroine-7

Heroin is synthesized by the acetylation of the two hydroxyl groups (highlighted blue and red) with acetyl chloride.
external image heroin.gif
Strucural Diagram of Heroin with highlighted functional groups the acetyl groups that replaced the hydroxyl groups-8

-The replacement of the –OH groups in morphine creates Heroin.

-Heroine is less soluble in water than morphine, and thus it is more soluble in non-polar solvents such as oils and fats.

-Because it’s now more non-polar, heroin can be injected intravenously, where it can quickly flow through the blood and brain barriers that normally prevent the passage of polar and large molecules.

-Because it’s taken this way, heroin is much more potent and effective than morphine. The effect lasts for a short while however, for once heroin is absorbed, the acetyl groups are removed and morphine is recreated.


Objective 1:
Picture 1- http://itech.dickinson.edu/chemistry/wp-content/uploads/2008/04/penicillin-core1.png
Picture 2- http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit2/control/blactam.html
Picture 3- http://lecturer.ukdw.ac.id/dhira/BacterialStructure/images/Peptoglycan.jpg
Picture 4+5- (Screenshots of video found on B-Lactam Resistance on http://www.mechanismsinmedicine.com/default.aspx)
Picture 6- http://www.crestock.com/images/contest2007/3779-2-crestock%20balloon%20burst.jpg

Objective 2:
Picture 7- http://www.ch.ic.ac.uk/rzepa/mim/drugs/gifs/morphine.gif
Picture 8- http://www.ch.ic.ac.uk/rzepa/mim/drugs/gifs/heroin.gif