Navigation Links
Anthrax inhibitor counteracts toxin, may lead to new therapeutics

Researchers from Rensselaer Polytechnic Institute and the University of Toronto have designed a nanoscale assembly of molecules that successfully counteracts and inhibits anthrax toxin in animal and laboratory experiments. The novel approach used to neutralize anthrax toxin could be applied in designing potent therapeutics for a variety of pathogens and toxins, according to the researchers.

Anthrax toxin, secreted by the anthrax bacterium, is made of proteins and toxic enzymes that bind together to inflict damage on a host organism. The inhibitor, which is described by the Rensselaer-Toronto team in the April 23 online edition of the journal Nature Biotechnology, works by preventing the assembly of toxic enzyme components, thereby blocking the formation of fully assembled anthrax toxin and neutralizing its activity.

The inhibitor protected rats from anthrax toxin in the study.

"Our eventual goal is to use the inhibitor as a human therapeutic for anthrax exposure, one that can stop the toxin from functioning inside the body," says Ravi Kane, the Merck Associate Professor of Chemical and Biological Engineering at Rensselaer and a principal investigator of the project. "Combining the inhibitor with antibiotic therapy may increase the likelihood of survival for an infected person."

The 2001 intentional release of anthrax spores via postal mail in the United States led to increased research on possible therapeutics and vaccines to treat toxins that could be used as biological weapons. The current treatment for anthrax exposure is antibiotics, but inhalation anthrax still has a fatality rate of 75 percent even after antibiotics are given, according to the Centers for Disease Control and Prevention. Antibiotics slow the progression of infection by targeting the bacteria, but do not counter the advanced destructive effects of anthrax toxin in the body.

Anthrax toxin is a polyvalent protein complex in that it displays multiple copies of identical binding surfaces on the same structure. The inhibitor designed by the Rensselaer-Toronto team is also polyvalent and recognizes these surface patterns on the anthrax toxin molecular structure, allowing it to bind at multiple sites and become four orders of magnitude more potent than an inhibitor that binds to a single site.

"Think about how two Lego blocks snap together. A brick with four studs can interlock with a brick with four holes. These bricks will grip together better than if they had only one stud and one hole," says Jeremy Mogridge, Canada Research Chair and assistant professor of Laboratory Medicine and Pathobiology at the University of Toronto. "Furthermore, Lego works because the pattern of studs on one brick matches the pattern of holes on another."

Earlier work by other groups has shown that an inhibitor with a fixed pattern of chemical groups can recognize a protein with a similar fixed pattern of complementary groups. In this study, the team demonstrated that a therapeutic inhibitor displaying random patterns can recognize a target if its statistical characteristics match those of the toxin target. According to the researchers, endowing inhibitors with statistical pattern-matching capabilities is less difficult than designing inhibitors with fixed structures.

"The pattern matching-based approach used by our research team to neutralize anthrax toxin should be broadly applicable in designing potent therapeutics for a variety of pathogens and toxins, including influenza and HIV," says Kane.

The researchers tested their pattern-matching strategy by designing a polyvalent inhibitor for cholera toxin, demonstrating that this approach also could be used successfully to enhance the potency of polyvalent inhibitors directed to this target and, they suggest, others. They note the work also could be useful for creating specific target recognition in biological sensors.

The team says their work demonstrates fo r the first time that liposome-based polyvalent inhibitors are effective in animals and they are continuing development on the anthrax inhibitor through additional animal testing.


'"/>

Source:Rensselaer Polytechnic Institute


Related biology news :

1. Study Models Impact Of Anthrax Vaccine
2. Anthrax test, developed by army and CDC, receives FDA approval
3. Anthrax inhibitors identified by Burnham team
4. Anthrax stops body from fighting back, study shows
5. Anthrax spores may survive water treatment
6. Anthrax attack posed greater potential threat than thought
7. Anthrax paralyzes immune cells with lethal toxin, UF research shows
8. Protease inhibitors reach beyond HIV
9. UNC scientists discover new role for protein as fundamental inhibitor of cell movement
10. Small molecule inhibitor of cholera discovered
11. Enzyme inhibitors block replication of SARS virus
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/7/2017)... 2017   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that the latest ... highly flexible and award winning eClinical solution, is now ... is a proven Software-as-a-Service (SaaS) clinical research technology ... but also delivers an entire suite of eClinical tools ...
(Date:2/7/2017)... 2017 Ipsidy Inc. ( www.ipsidy.com ... IDGS], ("Ipsidy" or the "Company") a provider of secure, ... is pleased to announce the following changes as part ... January 31, 2017, Philip D. Beck was ... President.  An experienced payment industry professional and public company ...
(Date:2/3/2017)... , Feb. 3, 2017  Texas Biomedical Research Institute ... Larry Schlesinger as the Institute,s new President ... Biomed effective May 31, 2017. He is currently the Chair ... of the Center for Microbial Interface Biology at Ohio State ... as the new President and CEO of Texas Biomed," said ...
Breaking Biology News(10 mins):
(Date:2/15/2017)...  Trianni, Inc. („TRIANNI") gab heute bekannt, man ... über die Verwendung der The Trianni Mouse unterschrieben, ... Entdeckung monoklonaler Antikörper. Die Trianni Plattform ... das Janssen den Zugang zu einer ... für die schelle Isolierung vollständig menschlicher Therapeutika optimiert ...
(Date:2/15/2017)... 2017  Vanda Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA), ... fourth quarter and full year ended December 31, ... for Vanda as we continued to demonstrate strong ... exclusivity for Fanapt," said Mihael H. Polymeropoulos, M.D., ... pipeline with important 2017 milestones underscores Vanda,s commitment ...
(Date:2/15/2017)... Feb. 15, 2017 Windtree Therapeutics, Inc. (Nasdaq: ... developing aerosolized KL4 surfactant therapies for respiratory diseases, will ... presentation) at 8:00 AM EST on Thursday, February 16, ... clinical program, the recently announced closing of a $10.5 ... To participate in the live call and ...
(Date:2/15/2017)... ... February 15, 2017 , ... Diameter Health ... Diameter Health technology in the hands of Lantana analysts. The high-performance platform of ... and public health entities – all those mining value from clinical data – ...
Breaking Biology Technology: