Current Topics in Chemistry - Bruice

Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 25. Nucleosides, Nucleotides, and Nucleic Acids.

For each of the following questions, please refer to the following article:

DRUG-RESISTANT SALMONELLA INFECTIONS INCREASING, STUDY SAYS
by Richard Saltus (The Boston Globe, May 7, 1998)

Editorial Comments

Earlier, in the news item accompanying chapter 16, we studied an article on drug resistant bacteria with a focus on penicillin and its mode of action. With the present article, we want to revisit the topic and add some detail as to what types of antibiotics there are. The US Food and Drug Administration describes the The Rise of Antibiotic-Resistant Infections in an article posted at their website and you might want to read that article as well.

In general, an "antibiotic" is any substance that harms or kills a microorganism. We usually use the term "antibiotic" in a more restricted sense to describe chemicals that harm or kill bacteria. These antibiotics should inhibit some process that is completely unique to bacteria and necessary for the bacterium to remain alive. Take a look at John Brown's "What the Heck is an Antibiotic?" site.

Penicillin kills bacteria by interfering with the ability to synthesize cell walls. It is thought that penicillin reacts with an enzyme that is essential to make cell walls. This enzyme contains an alcohol function which can react with the beta-lactam moiety of the penicillin. This reaction inactivates the enzyme. Growing cells die if they cannot produce cell walls. A truly impressive illustration as to how penicillin kills Escherichia Coli bacteria can be found on the Cells Alive! page on penicillin. Do watch the quicktime movie.

There are many other ways to kill bacteria and these intefer with bacteria growth by way of preventing "translation". Translation is the process by which the information contained in mRNA (transcripted from DNA) is decoded and employed to build proteins. This process takes place in the ribosomes and involves the reaction of the amino group of an amino acid bound to a tRNA to an ester of the peptide on the adjacent tRNA via an enzyme-catalyzed nucleophilic acyl substitution reaction. Several antibiotics interfere with this biosynthesis: (1) Tetracycline prevents the aminoacyl-tRNA from binding to the ribosome. (2) Erythromycin prevents elongation of the protein by preventing the tRNA from moving from the A site to the P site. (3) Streptomycin binds to the 30S ribosome and inhibits the initiation of translation. (4) Chloramphenicol prevents the new peptide bond from being formed because it binds to acetyltransferase.

The mode of action of the antibiotic chloramphenicol is illustrated by the X-ray structure of an acetyltransferase bound chloramphenicol molecule.

Pertinent Text References
Chapter 16. Box on "The Discovery of Penicillin".
Chapter 16. Box on "Penicillin and Drug Resistance".
Chapter 16. Box on "Penicillin in Clinical Use".
Chapter 16. News Item Accompanying Chapter 16.
Chapter 25. Nucleosides, Nucleotides, and Nucleic Acids.
Chapter 25.13. Biosynthesis of Proteins: Translation.
Chapter 25. Box on "Antibiotics That Act by Inhibiting Translation".

Questions

Question 1: Know your enemy: View the Bacteria Cam: Growth of Streptococcus pneumoniae. Observe and "measure" the doubling period of these bacteria.

Answer 1: Less than 14 minutes.

Question 2: Examine the X-ray structure of the acyltransferase with bound chloramphenicol and write down the structural formula of chloramphenicol as far as possible (the X-ray structure does not show H-atoms). Complete the structural formula by comparison to the ChemFinder.

Answer 2: Given by ChemFinder.

Question 3: What are the steps involved in the biosynthesis of proteins?

Answer 3: Bruice 3/e, Chapter 25.13.

Question 4: What is the function of the enzyme "acetyltransferase" in the biosynthesis of protein and what is the consequence of its inhibition?

Answer 4: Bruice 3/e, Chapter 25.13.

Chemistry & Society.
Under the headline New Molecular Targets For Cancer Therapy, Allen Oliff, Jackson B. Gibbs and Frank McCormick report in the Scienfic American article about therapies of the future. Many of these strategies involve the inhibition of specific enzymes involved in protein bio-synthesis.