Seite - (000257) - in Biomedical Chemistry: Current Trends and Developments

Many drugs see medicinal application denied due to physical, pharmacokinetic or pharmacodynamic properties. The use of different strategies to improve solubility, stability, permeability and targeting problems in drug discovery and development is crucial. The implementation of a prodrug approach in the early stages of drug discovery is a growing trend. Prodrugs are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation to release the parent drug. There are several promoieties that can be use in prodrug design, where the selection of a specific promoiety is essential. The ultimate goal is a chemically stable prodrug that does not generate toxic metabolites after bioconversion. Some of these works were based on amino acid applications. Amino acids are basic constituents of a cell structure and require specialized transport systems to cross the plasma membrane. Over the past few years, several amino acid transport systems have been identified and classified on the basis of their substrate affinity, dependence on sodium ions, energy and pH. The low toxicity of amino acids makes them attractive carriers for the development of prodrugs for poorly absorbed therapeutic agents. To make the prodrug a substrate for carrier mediated transport, an amino acid promoiety also balances the water solubility of the prodrug. New synthetic strategies for limiting metabolism and alternative routes of administration have emerged in recent years and resulted in a large number of peptide-based drugs now being marketed. Peptide- based drug discovery could be a serious option for addressing as-of-yet unresolved problems. New peptide therapeutics are delivering significant commercial value in a broad range of indications including expanding markets such as diabetes and oncology, as well as orphan indications. Developments in solid-phase peptide synthesis (SPPS) using Fmoc chemistry have led to larger peptide molecules and small proteins being accessible by chemical synthesis on scales of multiple kg. The great advantage of SPPS over solution-phase synthesis is the simplicity, readiness and efficiency of the synthetic process. In solution-phase synthesis, each synthetic intermediate has to be isolated and purified after every reactional step, which leads to a very expensive and time consuming process. Furthermore, it is not convenient to use a large