Navigation Links
Caltech researchers increase the potency of HIV-battling proteins
Date:7/29/2011

PASADENA, Calif.If one is good, two can sometimes be better. Researchers at the California Institute of Technology (Caltech) have certainly found this to be the case when it comes to a small HIV-fighting protein.

The protein, called cyanovirin-N (CV-N), is produced by a type of blue-green algae and has gained attention for its ability to ward off several diseases caused by viruses, including HIV and influenza. Now Caltech researchers have found that a relatively simple engineering technique can boost the protein's battling prowess.

"By linking two cyanovirins, we were able to make significantly more potent HIV-fighting molecules," says Jennifer Keeffe, a staff scientist at Caltech and first author of a new paper describing the study in the Proceedings of the National Academy of Sciences (PNAS). "One of our linked molecules was 18 times more effective at preventing infection than the naturally occurring, single protein."

The team's linked pairs, or dimers, were able to neutralize all 33 subtypes of HIV that they were tested against. The researchers also found the most successful dimer to be similar or more potent than seven well-studied anti-HIV antibodies that are known to be broadly neutralizing.

CV-N binds well to certain carbohydrates, such as the kind found in high quantities connected to the proteins on the envelope that surrounds the HIV virus. Once attached, CV-N prevents a virus from infecting cells, although the mechanism by which it accomplishes this is not well understood.

What is known is that each CV-N protein has two binding sites where it can bind to a carbohydrate and that both sites are needed to neutralize HIV.

Once the Caltech researchers had linked two CV-Ns together, they wanted to know if the enhanced ability of their engineered dimers to ward off HIV was related to the availability of additional binding sites. So they engineered another version of the dimersthis time with one or more of the binding sites knocked outand tested their ability to neutralize HIV.

It turns out that the dimers' infection-fighting potency increased with each additional binding sitethree sites are better than two, and four are better than three. The advantages seemed to stop at four sites, however; the researchers did not see additional improvements when they linked three or four CV-N molecules together to create molecules with six to eight binding sites.

Although CV-N has a naturally occurring dimeric form, it isn't stable at physiological temperatures, and thus mainly exists in single-copy form. To create dimers that would be stable under such conditions, the researchers covalently bound together two CV-N molecules in a head-to-tail fashion, using flexible polypeptide linkers of varying lengths.

Interestingly, by stabilizing the dimers and locking them into a particular configuration, it seems that the group created proteins with distances between binding sites that are very similar to those between the carbohydrate binding sites in a broadly neutralizing anti-HIV antibody.

"It is possible that we have created a dimer that has its carbohydrate binding sites optimally positioned to block infection," says Stephen Mayo, Bren Professor of Biology and Chemistry, chair of the Division of Biology, and corresponding author of the new paper.

Because it is active against multiple disease-causing viruses, including multiple strains of HIV, CV-N holds unique promise for development as a drug therapy. Other research groups have already started investigating its potential application in prophylactic gels and suppositories.

"Our hope is that those who are working to make prophylactic treatments using cyanovirin will see our results and will use CVN2L0 instead of naturally occurring cyanovirin," Keeffe says. "It has higher potency and may be more protective."


'/>"/>

Contact: Deborah Williams-Hedges
debwms@caltech.edu
626-395-3227
California Institute of Technology
Source:Eurekalert

Related biology news :

1. Think healthy, eat healthy: Caltech scientists show link between attention and self-control
2. Caltech researchers create the first artificial neural network out of DNA
3. Caltech scientist awarded $5 million grant for plant research
4. Caltech researchers build largest biochemical circuit out of small synthetic DNA molecules
5. 2011 HFSP Nakasone Award for Michael Elowitz of Caltech
6. Young Caltech engineers recognized for innovative work in disease diagnostic technologies
7. Tip sheet: Caltech researchers presenting at AAAS
8. Caltech-led team creates damage-tolerant metallic glass
9. Caltech scientists describe the delicate balance in the brain that controls fear
10. NIH awards $11.5 million for new Caltech-led membrane-protein center
11. Caltech chemists develop simple technique to visualize atomic-scale structures
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: