© 2000 Prentice Hall. All rights reserved.

Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 20. Carbohydrates.


For each of the following questions, please refer to the following article:
BLOOD-THINNING DRUG FOUND USEFUL BEFORE ANGIOPLASTY
by Peter Modica (Medical Tribune News Service, January 31, 1998)


Editorial Comments

What do aspirin, nitroglycerin, and heparin have in common?" -- A pain relief medicine, an explosive and what?

Aspirin, nitroglycerin and heparin can cooperate to safe heart attack patients. Aspirin and nitroglycerin help widen arteries and heparin is a blood thinning drug. You already know the structures of aspirin and of nitroglycerine and we now want to take a look at heparin.

The polysaccharide heparin is a fairly complex molecule. Heparin contains subunits of glucosamine and uronic acids. Glucuronic acid and iduronic acid are common. The polymer is extensively sulfonated in that the C-6 OH groups of the glucosamine subunits are sulfonated, the C-2 OH groups of the iduronic acid subunits also are sulfonated, and some of the amino groups are sulfonated as well. Let's spend some time examining the structure so that we do in fact recognize the subunits and how they are connected. The following questions will get you started at thinking about what you are seeing.

The polysaccharide heparin is negatively charged and several types of counterions are used in medical formulations. Sodium heparin and calcium heparin are among the more frequently employed drugs.



Pertinent Text References
Chapter 20. Carbohydrates.
Chapter 20. Box on "Heparin".



Questions

Question 1: Heparin contains the subunits sulfated glucosamine (-OH replced by -NH2, glucuronic acid (-CH2-OH replaced by COOH) and iduronic acid (-CH2-OH replaced by COOH). State how these compounds differ from D-glucose and draw their structures. You might use the ChemFinder to find the answers.

Answer 1: Use the ChemFinder to find the answers.



Question 2: Examine the experimentally determined structure of heparin and write down in what sequence the various subunits occur. In the process, identify and count all sulfonate groups in the polymer.

Answer 2: Download the pdb file to your disk and open the file with molecular modeling software (e.g. Chem3D) for this analysis.



Question 3: Examine the glycosidic bonds between the sugar monomers. Examine only the glycosidic bonds on both ends of heparin. Do they have alpha and beta configuration?

Answer 3: Both are alpha.



Question 4: One of the striking features of the tertiary structure of heparin is simply that the polymer is rather straight. What feature of the molecule is responsible for this property of the tertiary structure?

Answer 4: The molecule contains a great number of negatively charged -NH-SO3- and -O-SO3- groups and these repel each other.



Chemistry & Society.
Did you ever wonder where drugs come from? Some are synthesized and others are taken from natural sources. Heparin is an intersting example to learn about the production of drugs using natural resources. If you follow either of the links "sodium haparin" or "calcium heparin", you will come across the following text. Translate this text into "English" and recognize how the drug heparin is produced. 

    SOURCES AND MANUFACTURING
    PROCESS

    Heparin is prepared from porcine
    intestinal mucosa. The method involves a
    proteolytic treatment, extraction and
    complexing with ion pairing reagents,
    followed by fractional precipitation and
    purification.