Page - (000216) - in Biomedical Chemistry: Current Trends and Developments

amine or α-carboxylic group of an amino acid is attached to parent functional groups (hydroxyl, amine, and carboxyl). α-Amine or α- carboxylic groups of amino acid can also be linked to the parent drug via carbonate and carbamate links. The use of amino acid side chains, which offer wealth of functional groups (e.g. amine, carboxylic acid, alcohol, thiol) as prodrug handles presents tremendous opportunities in prodrug design. While in most cases amino acids are directly conjugated to the parent drugs, bifunctional linkers have been used to further increase the structural diversity and types of parent drugs that could be linked to amino acids (Gupta, 2009; Cao, 2012). Table 3.1.1: Advantages of using amino acids in drug development (adapted from Vig, 2013). Advantage • Large structural diversity • Wide-range of functional groups for attachment to parent drug • α-Amine and α-carboxylic group • Well established prodrug chemistry • Commercial availability • Fewer safety concerns • Substrates for various intestinal influx transporters • Availability of commercially successful amino acid prodrugs • Used to improve pharmaceutical properties of marketed drugs or difficult compounds Rationale • 20 common natural amino acids • A number of other naturally occurring amino acids