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Manmade antibodies hold biomedical promise
Date:5/19/2010

n 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.

The strategy relies on the fact that the binding affinity of two such amino acid sequences is the product of their combined affinity, allowing two peptides with weak attraction to a given protein to be joined to produce a synbody with strong binding properties. Remarkably, the assemblage of both the individual peptides and the synbody are carried out randomly.

The raw material for the synbody comes from a library of 10,000 peptides, with each amino acid sequence randomly composed. As Johnston explains, "the randomness turned out to be the key to all of this, because a random sequence has more flexibility and degrees of freedom than life sequences do." Each resulting linear peptide chain is able to find 2 or 3 points of contact with virtually any protein. When two such peptides are combined to form a synbody, a high-affinity ligand is produced, displaying specificity for a given protein.

Currently, the only limiting technological consideration is the number of proteins that can be placed on an array slide and that capability, as Johnston notes, is rapidly improving. Another key advantage in the use of synbodies is that they remain stable over time, unlike their biological counterparts, making them far more suitable for diagnostic assays.

Exposing random synbodies to multiple proteins helps build a library of effective ligands over time. To create a synbody to a particular disease protein o
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Contact: Joe Caspermeyer
joseph.caspermeyer@asu.edu
480-258-8972
Arizona State University
Source:Eurekalert

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