modifications to the peptide backbone that enhance stability and targeting
The human body employs endogenous peptides and small proteins to facilitate cell signalling pathways, most notably as hormones. While peptide pharmaceuticals offer attractive pharmacologic properties, such as tight binding, high solubility and low toxicity, their utility is tempered due to their low metabolic stability and their recognition by clearance mechanisms. To overcome these challenges, peptide chemists have developed a toolkit of relatively simple modifications that can be made to the peptide backbone, including both the N- and C-termini. These modifications can not only impart stability on the peptide but can also aid in the targeting and binding of the peptide to its biological target.
Many biochemical processes within the human body rely upon an elaborate network of endogenous signalling molecules and their associated receptor sites. One of the most important signalling molecules that our bodies employ are peptides. Like proteins and enzymes, peptides are composed of linear sequences of amino acids but are typically smaller in size and have more conformational flexibility. Bioactive peptides are highly regulated, not only in their biosynthesis and their storage, such as preprohormones, but especially in the release of the active peptide. Many of these natural peptides have been designed by Nature to not only be incredibly fast acting on the target receptor, but also cleared from the bloodstream rapidly.
As the recent past has shown, peptide pharmaceuticals are a rapidly growing area of research and development. It has been demonstrated that in many cases, the innate advantages of peptides over small-molecule pharmaceuticals, including high solubility, high specificity and low toxicity, can more than make up for their short-falls of low bioavailability and metabolic instabilities.
Much like endogenous pepti ...