Artificial antibodies hold biomedical promise

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ANTIBODIES are the immune system’s warriors. Their role is to pinpoint disease pathogens, attaching to them and neutralizing their effects. Though antibodies are of great value for biomedical research, the process of creating them has been time-consuming and tedious. Researchers at the Biodesign Institute at Arizona State University have developed a much faster and simpler way of making synthetic antibodies, by carrying out the usual steps in reverse.
Stephen Albert Johnston and Chris Diehnelt of Biodesign’s Center for Innovations in Medicine at Arizona State University, along with their colleagues, have developed a technique for constructing amino acid sequences, then linking them together to form a synthetic antibody, or synbody, that can bind with one or more protein molecules contained in the vast repository of human proteins — the proteome.
The group has developed a high affinity synbody capable of binding with AKT-1, a critical protein believed to play a role in aging, obesity, and cancer.
In addition to the potential of synbodies to directly target proteins associated with disease-causing microbes, they also show great potential as a research tool and building block for novel diagnostics and treatments. The team’s findings appear in the current issue of the journal PLoS ONE.
As Johnston notes, traditional antibodies are already in wide use for biological research, but the existing procedures for producing them are laborious and costly. “Traditional antibodies are made by taking the protein you want to bind,” Johnston says, “and injecting it into an animal, which responds by making antibodies.” These antibodies, or the cells that produce them, are then extracted.
Rather than beginning with a protein in order to produce an antibody, the new technique involves building an antibody first.
“We turn the whole process on its head, making the antibody chemically, then finding out what it’s an antibody to,” Johnston says.
To accomplish this, a 20-unit random sequence of amino acids are joined together like beads on a necklace to form a peptide.
By uniting two of these peptide chains, linked together by means of a chemical scaffold, a binding molecule or ligand is created, which can attach to a specific protein with high affinity. The resulting synbody may then be screened against a multitude of human proteins, to find its mate.