Featured Research

from universities, journals, and other organizations

Compound Has Potential For New Class Of AIDS Drugs

Date:
May 19, 2008
Source:
University of Michigan
Summary:
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.

Image of the molecule researchers discovered that keeps the flaps from closing on the HIV-1 protease. It inhibits the flaps from closing, and prevents the protease from assembling an active virus.
Credit: Kelly Damm

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 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."


Story Source:

The above story is based on materials provided by University of Michigan. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kelly L. Damm, Peter M. U. Ung, Jerome J. Quintero, Jason E. Gestwicki, Heather A. Carlson. A poke in the eye: Inhibiting HIV-1 protease through its flap-recognition pocket. Biopolymers. Volume 89, Issue 8 , Pages 643 - doi: 652.10.1002/bip.20993 [link]

Cite This Page:

University of Michigan. "Compound Has Potential For New Class Of AIDS Drugs." ScienceDaily. ScienceDaily, 19 May 2008. <www.sciencedaily.com/releases/2008/05/080514171758.htm>.
University of Michigan. (2008, May 19). Compound Has Potential For New Class Of AIDS Drugs. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2008/05/080514171758.htm
University of Michigan. "Compound Has Potential For New Class Of AIDS Drugs." ScienceDaily. www.sciencedaily.com/releases/2008/05/080514171758.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Nigeria Ups Ebola Stakes on 1st Death

Nigeria Ups Ebola Stakes on 1st Death

Reuters - Business Video Online (July 29, 2014) Nigerian authorities have shut and quarantined a Lagos hospital where a Liberian man died of the Ebola virus, the first recorded case of the highly-infectious disease in Africa's most populous economy. David Pollard reports Video provided by Reuters
Powered by NewsLook.com
Running 5 Minutes A Day Might Add Years To Your Life

Running 5 Minutes A Day Might Add Years To Your Life

Newsy (July 29, 2014) According to a new study, just five minutes of running or jogging a day could add years to your life. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Poses Little Threat To U.S.: CDC

Ebola Outbreak Poses Little Threat To U.S.: CDC

Newsy (July 29, 2014) The Ebola outbreak in West Africa poses little threat to Americans, according to officials with the Centers for Disease Control and Prevention. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins