Seite - (000295) - in Biomedical Chemistry: Current Trends and Developments

Rebecca Fransson, Christian Sköld and Anja Sandström* 3.3 Strategies for Conversion of Peptides to Peptidomimetic Drugs 3.3.1 Peptides as Starting Points in Drug Discovery Due to their importance in many biological functions, bioactive peptides are interesting as starting points in drug discovery and as valuable research tools in initial investigations of the biological mechanisms of various diseases (Sewald, 2002). A compound intended as an oral therapeutic agent should display not only the desired effect (pharmacodynamics), but also satisfying pharmacokinetic criteria (Fig 3.3.1). Thus, adsorption, distribution, metabolism and excretion (ADME) properties play a critical role in defining a good drug candidate. However, due to the structural characteristics of peptides, they suffer from inherent drawbacks, such as low bioavailability, low metabolic stability, poor absorption from the gastrointestinal tract (GI), and poor brain exposure as a result of low permeability over the blood-brain barrier (BBB) (Humphrey, 1986; Veber, 1985). Figure 3.3.1: Drug distribution in the human body is determined by its ADME properties. Furthermore, peptides have a large degree of conformational flexibility, and can fold into complex tertiary structures crucial for their molecular recognition and their ability to produce a biological response. In order to fully benefit from the potential of biologically active peptides in