Featured Research

from universities, journals, and other organizations

A Possible New Way To Block HIV Infection Of Healthy Cells Discovered

Date:
May 16, 2002
Source:
University Of Illinois At Urbana-Champaign
Summary:
An experiment to understand how chemokine peptides dock to a receptor on a cell wall – a pivotal connection that allows HIV to infect healthy cells – has yielded an unexpected fundamental discovery and a possible new way to block AIDS.

CHAMPAIGN, Ill. — An experiment to understand how chemokine peptides dock to a receptor on a cell wall – a pivotal connection that allows HIV to infect healthy cells – has yielded an unexpected fundamental discovery and a possible new way to block AIDS.

“There is still a lot to be done, but our findings provide new insights about the receptor’s flexibility and the potential mechanism of the interaction with HIV at the entry point of healthy cells,” said Ziwei Huang, a professor of biochemistry at the University of Illinois at Urbana-Champaign.

Huang was the principal investigator of the study, which appears in the May 17 issue of the Journal of Biological Chemistry. Huang’s team included researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia and Dana-Farber Cancer Institute at the Harvard Medical School in Boston.

Researchers used computer modeling to predict the structure of chemokine receptor-ligand bonding. Then they synthesized reverse-chirality D-peptides, based on a portion of amino-acid sequences of two natural L-proteins that bond to CXCR4, a chemokine receptor to HIV discovered in the mid-1990s. CXCR4 and CD4, a receptor identifed in the 1980s, are thought to act together to let HIV bond and insert its replicating machinery into cells.

Only in rare cases – and never involving membrane-class proteins – have reverse-chirality peptides bound at identical receptors. “We didn’t have any expectation that our synthesized peptide would bind to the CXCR4 receptor,” Huang said. “If you switch the chirality, you have a mirror-image change. You’d expect a different lineup of key amino-acid sidechains. We looked at this out of pure curiosity. We just wanted to see what would happen.

“Unexpectedly,” he said, “these D-peptides displayed strong binding and antagonistic activity toward CXCR4, thus revealing that the peptide binding site on CXCR4 is tolerant of changes in the chirality of ligands,” Huang said. “Normally, ligand receptor-bindings are very specific, just like putting your left hand in your left pants pocket.”

Not only were the D-peptides still recognized, they fit into the receptor more snugly than their natural L-peptide counterparts, blocking the virus from bonding. Subsequent experiments, documented in the paper, showed the synthetic D-peptides have a longer half life, making them less susceptible to biological decay than L-peptides.

In making the discovery, Huang designed and synthesized the D-peptide and tested its bonding to the receptor at Illinois. Testing against HIV-1 was done at Dana-Farber in Dr. Joseph Sodroski’s laboratory and by a group led by Hideko Kaji at Jefferson Medical College, where Huang had previously worked and had begun his research.

Traditional drug therapies have targeted protease or reverse transcriptase activity that occur after HIV has entered healthy cells. None stop HIV from docking with cells.

“Researchers realize that this approach is not enough,” Huang said. “It would be nice to have other targets. Our discovery suggests the possibility of a whole new therapeutic weapon, which alone or in combination with existing therapies could work better to block AIDS.”

Illinois authors on the paper, along with Huang, were James Pesavento, Chang-Zhi Dong, Youli Wang and Jing An. Co-authors from Thomas Jefferson University Medical College were Kaji, Naiming Zhou, Zhaowen Luo, Jiansong Luo, Xuejun Fan, Dongxiang Liu, Xiaobing Han and Megumi Hiraoka. Dana-Farber researchers were Mark Cayabyab and Sodroski.

The National Institutes of Health, Center for AIDS Research, G. Harold and Leila Y. Mathers Charitable Foundation, William F. McCarty-Cooper, Douglas and Judity Krupp, and Japan Science Foundation funded the research.


Story Source:

The above story is based on materials provided by University Of Illinois At Urbana-Champaign. Note: Materials may be edited for content and length.


Cite This Page:

University Of Illinois At Urbana-Champaign. "A Possible New Way To Block HIV Infection Of Healthy Cells Discovered." ScienceDaily. ScienceDaily, 16 May 2002. <www.sciencedaily.com/releases/2002/05/020516081128.htm>.
University Of Illinois At Urbana-Champaign. (2002, May 16). A Possible New Way To Block HIV Infection Of Healthy Cells Discovered. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2002/05/020516081128.htm
University Of Illinois At Urbana-Champaign. "A Possible New Way To Block HIV Infection Of Healthy Cells Discovered." ScienceDaily. www.sciencedaily.com/releases/2002/05/020516081128.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. 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