Seite - (000215) - in Biomedical Chemistry: Current Trends and Developments

adenosylmethionine (Lu & Mato, 2012). Deriving from Cys, taurine (2- aminoethanesulfonic acid) is the most abundant amino acid in mammals. Being widely distributed in the CNS, second only to glutamate in concentration, its concentration differs depending on the regions of the brain, brain activity and animal species studied. It also presents different functions, which have been studied for their potential in neurology as a trophic factor in brain development, regulating calcium transport, in the integrity of the eardrum, as an osmoregulator, neurotransmitter and neuromodulator as well as for its neuroprotective action (Wu & Prentice, 2010). 3.1.2 Amino Acids and Drug Development All α-amino acids except glycine have a chiral α-carbon and can exist in two optical isomers, L-form and D-form. The L-form of amino acids occurs naturally and prodrugs utilizing these amino acids are generally activated by naturally occurring enzymes. Both L- and D-amino acid prodrugs tend to have very similar physicochemical properties but the latter is generally more stable to hydrolysis by naturally occurring enzymes (Vig, 2003). This property of amino acids are often utilized by medicinal chemists to develop stable amino acid prodrugs. In addition to the natural amino acids and their D-forms, extensive arrays of synthetic amino acids and di-/tri-peptides are commercially available for medicinal chemists as promoieties (Ma, 2003). 3.1.2.1 Rationale for Drug Design Amino acids can be associated with drugs as a component of prodrug development. This association depends on the purpose of the prodrug, type of functional groups available on the parent drug, chemical and enzymatic conversion mechanisms of the prodrug to the parent drug and safety of the promoiety. Amino acids as promoieties ease manufacturing and offer several other advantages (Table 3.1.1; Vig, 2013). Most amino acid prodrugs are either esters or amides, in which the α-