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Protein aggregation

Harnessing the power of a universal innate mechanism

Proteins are continuously being manufactured by our cells and quality control mechanisms exist to ensure that misfolded or dysfunctional proteins are removed. Aggregated proteins, or ordered intermolecular protein arrangements, are processed and degraded by the cell’s clearing mechanisms.

Sequence and structure-specific seeding of aggregation
Short sequences that promote this aggregation process, called ‘aggregation prone regions’ (APRs), have been identified inside almost all proteins. These APRs have a tendency to self-associate into ordered intermolecular arrangements and stick to one another if they encounter a matching sequence. The self-assembly of APRs can drive protein aggregation only in situations where proteins are partially or completely unfolded, and the APRs are exposed, for example during protein translation.

Using APRs as barcodes to target proteins
80% of all proteins possess at least one APR and most APRs are unique in their sequence of amino acids. The Pept-in technology capitalizes on this natural protein aggregation process by aiming to induce aggregation of selected target proteins through seeding with a synthetic peptide containing a bait sequence that matches the APR sequence present in the target protein.

This means that almost any protein can be functionally knocked-down using Pept-ins, independent of structural or functional protein class, without the need for an active site or an epitope on which small molecule drugs and biologicals rely.