Antibody like Capture Agents using Peptide library and Click Chemistry

Recently I wrote about Integrated Barcode Biochips that combines on-line separation of plasma from blood samples with antibody patterning using DNA for multiplexed assay. The Achilles heel of this technology and every other biosensing platform is the instability of biological component. Now James Heath who developed Barcode Biochips is working on replacing antibodies altogether by something more robust and less expensive. His latest effort uses in-situ click chemistry to assemble peptide libraries with antibody like binding properties for proteins-bovine carbonic anhydrase in this case. The process is iterative and starts with one bead and one compound (OBOC) hepta-peptide library and selects a weakly binding ligand (500µM affinity for protein). The ligand is identified and synthesized with acetylene end group and incubated with OBOC library containing peptide with azide end group. The click chemistry results in biligand that are then screened for binding. End result is biligand with improved affinity constant of 3µM for protein. Repeat of the same process result in triligand with affinity constant of 64nM. Once identified, the triligand capture agents should be stable and inexpensive to synthesize in large quantities and easier to QC for purity, activity.

Now this is not the first foray into antibody like capture agents (see a list of artificial antibody like capture agents here) and certainly will not be last. However, concept is attractive and goal is worthy of pursuing.


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