We performed the screening and selection of variants from a 12-mer peptide phage-display library to identify 12-mer peptides that are capable of binding to thermally-derived aggregates of bovine carbonic anhydrase (BCA). The purpose was to see whether any of the identified peptides could be synthesized and tested for the ability to interfere with aggregation, the underlying hypothesis being that thermal aggregation involves the coming-together of partially unfolded protein unfolding intermediates, and that by screening a phage-displayed peptide library we could potentially identify peptides capable of binding to the BCA aggregates which would also be capable of binding to BCA molecules undergoing aggregation, to sterically interfere with aggregation. We identified peptides that reduced aggregation, but we also identified peptides that increased aggregation. Our interpretation was that the peptides that reduced aggregation were capable of binding to surfaces that are partially involved in aggregation, such that binding would sterically block aggregation. With the other peptides which increased aggregation, our interpretation was that these peptides underwent binding to surfaces that are not involved directly in aggregation, such that by binding to such surfaces the peptides were somehow stabilizing the relevant partially-unfolded intermediates and increasing their lifetime, or survival, during thermal unfolding, resulting in an increase in the scope for thermal aggregation rather than a decrease.

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