Peptide-aptamers have several potential advantages over small molecules that make them attractive therapeutic agents:
1. Compared to small molecules and antibody approaches, the cycle-times to get to a potent active molecule are short (potentially as short as 8 weeks).
2. Peptide molecules can target different modes of inhibition (e.g. interfering with protein folding or protein:protein interaction) that are not tractable to treatment by small molecules.
3. Metabolism of peptide aptamers only yields naturally occurring amino acids and so the safety concerns associated with such molecules are greatly reduced compared to chemical xenobiotics.
Co-crystals of two peptide aptamers (white regions are the scafford – red regions are the variable regions) with a receptor extracellular domain (blue). The top co-crystal is showing indirect inhibition to ligand binding and the bottom crystal directly inhibits ligand binding (courtesy of Darren Tomlinson Leeds University).
Peptide aptamers are generally around 11 kilo Daltons in size and are extremely stable temperatures up to 100°C. The variable loop can be randomized generating complex libraries of greater than 1010 independent unique clones. Hits and leads are identified by a process of affinity selection screening using phage display or other screening modalities.
Blueberry is exploiting the potential of aptamers delivered using our nanopolymer drug delivery system to create a range of new nanomedicines.