Peptide-based pharmaceutical

At the age of genomics and proteomics, carbodiimide mediated protein engineering is of considerable importance. Natural proteins and enzymes are readily modified or crosslinked to influence their behavior. The carbodiimide mediated inter- or intramolecular crosslinking of proteins is highly useful because no foreign molecules are introduced. Carbodiimides are zero length crosslinkers. Peptide based pharmaceuticals use carbodiimides in their manufacture and this market will increase considerably over the current low level. 

The synthesis of peptides is an important area of dmg development. For many years, the high cost of peptide synthesis and the rapid degradation of peptides when administered in the body hampered the progress of peptide dmg discovery. Recent advances in peptide manufacturing and dmg delivery have increased the use of peptide-based pharmaceuticals. Two of the most prominent peptide dmgs are insulin and calcitonin. 

The most prominent field of applications for microchip—MS concerns identification and analysis of large molecules in the field of proteomics according to the reduced separation time compared to conventional approaches such as gel-based methods for protein analysis. High-throughput analyses, with lower contamination and disposability, are other features of microfabricated devices that allow the fast screening of proteomic samples in the clinical field. Applications also include the analysis of low-molecular-weight compounds such as peptides or pharmaceutical samples. 

Otvos, L., Jr., Cudic, M., Chua, B.Y., Deliyannis, G., and Jackson, D.C. (2004) An insect antibacterial peptide-based drug delivery system. Mol. Pharmaceut. 1, 220-232. 

Despite their favourable properties, peptide-based drugs are under-represented in the pharmaceutical market. This discrimination is usually due to their poor bioavailability, which sometimes necessitates non-oral administration or even special medical devices such as inhalers. Another related major disadvantage of peptides is their low metabolic stability due to proteolytic degradation, hi addition, costs of goods for the drug substance are sometimes tremendous. Therefore, there is considerable interest to transform the active principle of biologically active peptides into small molecules with improved pharmacokinetic properties, hi this chapter, we present an overview of... 

Glycopeptides are also being explored as drug candidates for other means. Addition of a carbohydrate to a peptide backbone often decreases proteolytic degradation and increases oral availability of peptide-based drugs. These are favorable qualities of pharmaceuticals that need to be optimized for agents to reach clinical trials. 

Self-assembled nanoparticulates comprise various kinds of polymeric, peptide-based, and lipoidal systems. The rationale for their pharmaceutical use is to incorporate the drug into the system and thereby modify its solubility or delivery. 

Five-membered ring heterocycles are common in numerous pharmaceuticals. In particular, the imidazole core structure, an element of histidine and its decarboxylation metabolite histamine, is often found [53]. The exceptional properties and wide applicability of the imidazole pharmacophore are due to its hydrogen-bond donor/acceptor capabilities and its high affinity for metals (present in many protein active sites, e.g., Zn, Fe, Mg) [54-58]. In addition, peptide-based protease inhibitors with improved pharmacokinetics and bioavailability have been obtained by replacing an amide bond with an imidazole [59]. 

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