Navigation Links
Potential drug molecule shows enhanced anti-HIV activity
Date:8/9/2012

Researchers from Munich and Naples have shown that minimal modification of a synthetic peptide with anti-HIV activity results in a new compound with more than two orders of magnitude higher binding affinity to the chemokine receptor CXCR4 and greatly improved anti-HIV activity. This could be a step toward the design of new, more effective drugs against AIDS, inflammatory diseases, and some forms of cancer.

Different strains of HIV-1 use either the chemokine receptor CCR5 or CXCR4 for entry into immune cells. While drugs that block usage of CCR5 by the virus are already available for anti-HIV therapy, no drugs have been approved that prevent the virus from using the CXCR4 receptor. Because the new cyclic peptide may be used to block CXCR4, it is a promising new drug candidate to block HIV-1 infections.

An international, interdisciplinary team including researchers in pharmaceutical radiochemistry and chemistry at the Technische Universitt Mnchen (TUM), a group of molecular modelers at the University of Naples, and virologists at the Helmholtz Zentrum Mnchen reported the results in Angewandte Chemie International Edition. This work was initiated by the radiochemists and organic chemists at TUM, who realized that their approach to modifying peptides as high-affinity CXCR4 ligands for imaging of cancers also has the potential to open a whole new area of drug research.

The researchers used a smart trick to augment both the binding affinity and the anti-HIV activity of an already known lead structure: They shifted one of the important side chains from the carbon to a neighboring nitrogen, thus fixing the skeleton of the molecule to present its binding groups in an improved orientation.

The cyclic structure of the peptide, with one unnatural D-amino acid (the mirror image of the natural amino acid tyrosine) and one so-called "peptoid" structure, makes the compound stable against enzymatic degradation and thus suitable for in vivo applications. Since CXCR4 receptors also play an important role in cancer metastasis, derivatives of this compound are also being tested as new agents for imaging and treatment of cancer. The team's "frozen peptoid" displays a 400 to 1500 times higher binding affinity to the CXCR4 ligand compared to other CXCR4-targeting compounds currently under clinical development, including one already involved in the treatment of non-Hodgkin lymphoma and multiple myeloma.

"We are very happy that the specific modifications designed by our team have led to a drug compound that may be useful for treatment of multiple life-threatening diseases," says Prof. Horst Kessler, a senior fellow of the TUM Institute for Advanced Study and "emeritus of excellence" in the TUM Department of Chemistry. "For anti-HIV therapy," adds Prof. Ruth Brack-Werner, a virologist from the Helmholtz Zentrum, "the new compound may provide a drug against particularly aggressive HIV-1 strains that come up in HIV-infected individuals after many years of infection." "We look forward with great enthusiasm to the next preclinical and clinical tests," says Prof. Hans-Jrgen Wester, TUM Chair of Pharmaceutical Radiochemistry. "These compounds offer exciting possibilities."


'/>"/>

Contact: Patrick Regan
regan@zv.tum.de
49-089-289-10515
Technische Universitaet Muenchen
Source:Eurekalert  

Related biology news :

1. Epigenetic signatures direct the repair potential of reprogrammed cells
2. New insight into mechanisms behind autoimmune diseases suggests a potential therapy
3. Interventional radiology: Potential breakthrough to treat mens enlarged prostate
4. Researchers report potential for a moderate New England red tide in 2012
5. Gallbladder shown as potential stem cell source for regenerative liver and metabolic disease
6. Researchers find potential dark side to diets high in beta-carotene
7. Beehive extract shows potential as prostate cancer treatment
8. Gene therapy for hearing loss: Potential and limitations
9. Folic acid food enrichment potentially protective against childhood cancers
10. Nuisance seaweed found to produce compounds with biomedical potential
11. Potential new approach to regenerating skeletal muscle tissue
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Potential drug molecule shows enhanced anti-HIV activity
(Date:4/17/2017)... , April 17, 2017 NXT-ID, Inc. (NASDAQ: ... announces the filing of its 2016 Annual Report on Form 10-K ... Commission. ... 10-K is available in the Investor Relations section of the Company,s ... the SEC,s website at http://www.sec.gov . 2016 Year ...
(Date:4/11/2017)... 2017 No two people are believed ... New York University Tandon School of Engineering and ... that partial similarities between prints are common enough ... phones and other electronic devices can be more ... lies in the fact that fingerprint-based authentication systems ...
(Date:4/5/2017)... April 4, 2017 KEY FINDINGS ... expand at a CAGR of 25.76% during the forecast ... the primary factor for the growth of the stem ... https://www.reportbuyer.com/product/4807905/ MARKET INSIGHTS The global stem cell ... application, and geography. The stem cell market of the ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... YORBA LINDA, CA (PRWEB) , ... October 11, ... ... adapted to upregulate any gene in its endogenous context, enabling overexpression experiments and ... activation (CRISPRa) system with small RNA guides is transformative for performing systematic gain-of-function ...
(Date:10/11/2017)...  VMS BioMarketing, a leading provider of patient support solutions, ... Educator (CNE) network, which will launch this week. The VMS ... care professionals to enhance the patient care experience by delivering ... health care professionals to help women who have been diagnosed ... ...
(Date:10/11/2017)... ... October 11, 2017 , ... ... granted orphan drug designation to SBT-100, its novel anti-STAT3 (Signal Transducer and Activator ... osteosarcoma. SBT-100 is able to cross the cell membrane and bind intracellular STAT3 ...
(Date:10/10/2017)... ... October 10, 2017 , ... Dr. Bob Harman, founder and CEO of ... Rotary Club. The event entitled “Stem Cells and Their Regenerative Powers,” ... Dr. Harman, DVM, MPVM was joined by two human doctors: Peter B. Hanson, ...
Breaking Biology Technology: