Peptides are an increasingly important class of drug. As natural ligands to many targets, they can combine agonistic or antagonistic activity with low toxicity risk and can be applied to disease targets, where small molecules or antibody-based drugs cannot be used. However, the number of therapeutic peptide drugs is held back by properties that are inherent to wild-type peptides. Namely, that they can often bind to multiple receptor subtypes and that the time they remain active in the body is usually very short. Lanthio Pharma’s innovative lanthipeptides overcome these problems and make it possible to discover highly target selective peptides, which only bind and activate one specific target subtype. Importantly, lanthipeptides are more stable than linear wild-type peptides and therefore have much better “drug-like” properties.
Creating receptor-selective peptides
A peptide can have different structural conformations, which can allow it to bind to several different receptors. One conformation is often optimal for binding to one specific receptor. Lanthio Pharma’s technology can be used to make lanthipeptides, which are selective for one specific receptor by constraining them in the optimal structural conformation for binding to that receptor. In this way we have already identified several selective and highly active agonistic peptides for various GPCR targets. This increased target selectivity can open up exciting new therapeutic applications around known disease targets.
Protection against degradation by enzymes in vivo
Peptides can be rapidly degraded by peptidases in the body, limiting their half-life and their therapeutic applicability. Lanthio Pharma’s technology not only constrains peptides in their optimal target binding conformation, the introduction of lanthionines also provides strong protection against peptidase degradation. As such, lantipeptides typically have better “drug-like” properties, compared to natural linear peptides. We use Lactococcus lactis bacteria to produce peptides of therapeutic interest. The lantibiotic enzyme system in Lactococcus lactis bacteria is then triggered to introduce one or more thioether bridges in specific locations in these peptides. Once the thioether bridges are formed, the lanthipeptides can be transported out of the bacteria and fixed to the cell wall to be displayed as part of a lantipeptide library, or be transported out of the bacteria into the extracellular medium to be easily purified.