Final Report Summary - PEPTIDEPADLOCK (Peptide padlocks evolved towards infinite affinity for antibody nanoassembly and ultrasensitive cell capture) Interactions between proteins normally depend on a range of non-covalent contacts. Under challenging conditions, such as with mechanical force or over long time-periods, non-covalent interactions often break. Unbreakable protein-protein interactions, linked by covalent bonding, provide many opportunities for robust connection of molecular building-blocks, including for biomaterials, enzymes and vaccines. When evaluating such unbreakable interactions, it is important to consider whether the reaction happens quickly even at low concentrations. This project has established a genetically-encoded peptide that reacts with its genetically-encoded protein partner with a speed close to the limit set by diffusion. We have shown that this interaction allows specific detection in a range of species. This interaction can also be combined with a similar unbreakable peptide/protein pair to generate a new class of protein team. We anticipate that the speed and simplicity of this reaction technology will provide many opportunities to generate new protein architectures, to enhance the detection of rare proteins and rare cells important in disease processes.
