University Wisconsin Madison

Here is some news for people who wish to hear more about HIV infection. Apparently researchers have designed synthetic protein-like mimics with the help of human immunodeficiency virus (HIV) and molecular engineering. By this they have supposedly claimed that they can stop unwanted biological conversations between cells.

Communications amongst proteins are extremely vital to numerous biological processes counting the ones which are of infections and tumor growth. Interactions both among the virus’s own protein cells and with the body cells so as to infect the cell are apparently important. And several viruses like HIV and others like influenza, Ebola and the severe acute respiratory syndrome (SARS) virus are examples of this case.

Samuel Gellman a chemistry professor at UW-Madison comments “There’s a lot of information transfer that occurs when proteins come together, and one would often like to block that information flow”.

Gellman’s UW-Madison research team includes former postdoctoral fellow W. Seth Horne who is now at the University of Pittsburgh and graduate student Lisa Johnson. They did some research on how to control protein shape. For that they conducted some laboratory experiments where they produced a set of peptide-like molecules which appear to have successfully blocked HIV infection of human cells.

The synthetic molecules after communicating with a piece of a vital HIV protein called gp41 actually put off the virus from contaminating the host cells. Gellman is of the opinion that this thought shows promise as an innovative opportunity to target other unwanted protein interactions.

Gellman states that previous efforts to put off the infection by selectively interfering with this communication have had very little success. Since most protein-protein interactions involve large molecular surfaces the drugs are not very successful in blocking them as they are small molecules. More than small molecules it is the short snippets of proteins or peptides are claimed to be more effective. The patients find it hard to manage as the small molecules are easily broken by enzymes and so they need frequent and large doses. These drawbacks can be evaded by the new synthetic approach by producing peptide-like molecules which has an adapted structure that degraded enzymes cannot recognize.

Gellman explains “We want to find an alternate language, an alternate way to express the information that the proteins express so that we can interfere with a conversation that one protein is having with another”

To improve the stability of the synthetic molecules at the same time preserving the three-dimensional shape essential to know and interact with the HIV gp41 protein, were maintained by Gellman and his colleagues who made structural tweaks to the backbone of their synthetic molecule. The resulting molecules called ‘foldamers’ are actually a fusion of natural and unnatural amino acid building blocks. It is a permutation that lets the scientists to direct shape, structure and stability with much better accuracy than at present is possible with natural amino acids alone.

The foldamer implements a shape that can cut short the protein-protein dialogue. Supposedly it also has the extra benefit of being highly resistant to degradation by naturally occurring enzymes, which are blocked by the foldamer’s atypical configuration. It means that at lower doses the molecule can remain effective for a longer period of time.

Gellman states “You don’t have to limit yourself to the building blocks that nature uses. There’s a huge potential here because the strategy we use is different from what the pharmaceutical and biotech industries now employ.”

Many of the synthetic foldamers displayed compelling antiviral action against HIV when used on cultured human cell lines in a dish. It is not apparent that foldamers can ever be used as anti-HIV drugs. But Gellman highlights that the results demonstrate that this type of approach has great potential to guide new ways to think about designing molecules for antiviral therapies and other biomedical applications.

This research appeared in the paper which appeared online this week (Aug 17) in the proceedings of the National Academy of Sciences.