Navigation Links
Compound has potential for new class of AIDS drugs
Date:5/14/2008

ANN ARBOR, Mich.---Researchers have developed what they believe is the first new mechanism in nearly 20 years for inhibiting a common target used to treat all HIV patients, which could eventually lead to a new class of AIDS drugs.

Researchers at the University of Michigan used computer models to develop the inhibiting compound, and then confirmed in the lab that the compound does indeed inhibit HIV protease, which is an established target for AIDS treatment. The protease is necessary to replicate the virus, says Heather Carlson, U-M professor of medicinal chemistry in the College of Pharmacy, and principal investigator of the study.

Carlson stresses this is a preliminary step, but still significant.

"It's very easy to make an inhibitor, (but) it's very hard to make a drug," said Carlson, who also has an appointment in chemistry. "This compound is too weak to work in the human body. The key is to find more compounds that will work by the same mechanism."

What's so exciting is how differently that mechanism works from the current drugs used to keep the HIV from maturing and replicating, she says. Current drugs called protease inhibitors work by debilitating the HIV-1 protease. This does the same, but in a different way, Carlson says.

A protease is an enzyme that clips apart proteins, and in the case of HIV drugs, when the HIV-1 protease is inhibited it cannot process the proteins required to assemble an active virus. In existing treatments, a larger molecule binds to the center of the protease, freezing it closed.

The new mechanism targets a different area of the HIV-1 protease, called the flap recognition pocket, and actually holds the protease open. Scientists knew the flaps opened and closed, but didn't know how to target that as a mechanism, Carlson says.

Carlson's group discovered that this flap, when held open by a very small molecule---half the size of the ones used in current drug treatments---also inhibits the protease.

In addition to a new class of drugs, the compound is key because smaller molecules have better drug-like properties and are absorbed much more easily.

"This new class of smaller molecules could have better drug properties (and) could get around current side effects," Carlson said. "HIV dosing regimes are really difficult. You have to take medicine several times in the day. Maybe you wouldn't have to do that with these smaller molecules because they would be absorbed differently."

Kelly Damm, a former student and now at Johnson & Johnson, initially had the idea to target the flaps in this new way, Carlson says.

"In a way, this works like a door jam. If you looked only at the door when it's shut, you'd not know you could put a jam in it," she said. "We saw a spot where we could block the closing event, but because everyone else was working with the closed form, they couldn't see it."


'/>"/>

Contact: Laura Bailey
baileylm@umich.edu
734-647-1848
University of Michigan
Source:Eurekalert

Related biology news :

1. Chemical compound prevents cancer in lab
2. UF scientists discover compound that could lead to new blood pressure drugs
3. UDs Bobev receives NSF Early Career Award for research on novel compounds of rare Earth metals
4. A compound extracted from olives inhibits cancer cells growth and prevents their appearance
5. Protein protects brain against compound in lead poisoning, liver disease
6. New form of compound stimulates research on hydrogen storage
7. Natural compound in broccoli could treat devastating genetic skin disorder
8. Synthetic compound promotes death of lung-cancer cells, tumors
9. Chemical compound present in detergents produce bacteria alterations in agricultural soils
10. Naturally-occurring apple compounds reduce risk of pancreatic cancer
11. New microsensor measures volatile organic compounds in water and air on-site
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... First quarter 2016:   , Revenues amounted ... quarter of 2015 The gross margin was 49% (27) ... the operating margin was 40% (-13) Earnings per share ... operations was SEK 249.9 M (21.2) , Outlook   ... M. The operating margin for 2016 is estimated to ...
(Date:4/15/2016)...  A new partnership announced today will help ... in a fraction of the time it takes ... life insurance policies to consumers without requiring inconvenient ... Diagnostics, rapid testing (A1C, Cotinine and HIV) and ... weight, pulse, BMI, and activity data) available at ...
(Date:3/31/2016)... 2016   LegacyXChange, ... "Company") LegacyXChange is excited to release its ... to be launched online site for trading 100% guaranteed ... will also provide potential shareholders a sense of the ... an industry that is notorious for fraud. The video ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... On Wednesday, June 22, 2016, the ... the Dow Jones Industrial Average edged 0.27% lower to finish ... 0.17%. Stock-Callers.com has initiated coverage on the following equities: Infinity ... NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ... ). Learn more about these stocks by accessing their free ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance ... consulting, provides a free webinar on Performing Quality Investigations: Getting to ... 12pm CT at no charge. , Incomplete investigations are still a major concern ...
(Date:6/23/2016)... FRANCISCO , June 22, 2016  Amgen (NASDAQ: ... sponsorship of the QB3@953 life sciences incubator ... human health. The shared laboratory space at QB3@953 was ... overcome a key obstacle for many early stage organizations ... part of the sponsorship, Amgen launched two "Amgen Golden ...
(Date:6/22/2016)... 22, 2016 Cell Applications, Inc. and ... to produce up to one billion human induced ... one week. These high-quality, consistent stem cells enable ... and spend more time doing meaningful, relevant research. ... high-volume manufacturing process that produces affordable, reliable HiPSC ...
Breaking Biology Technology: