The use of uncoded alpha-amino acids residues in drug design

摘要

Structure-activity relationship (SAR) studies in bioactive peptides have as main objective the understanding of biological phenomena at molecular level with the aim to produce and possibly develop new materials relevant to pharmacology and medicinal chemistry, which might mimic biological processes by enhancing or somehow modulating their effects. The peptide pharmaceutical targets of these studies have been among others hormones, enzymes, transport systems, neurotransmitters, ion channel ionophores antibiotics, sweeteners, etc.. The number of native and modified peptides used as drugs is constantly increasing. However, the use of peptides as drugs is limited by the following factors: a) their low metabolic stability towards proteolysis in the gastrointestinal tract and in serum; b) their poor absorption after oral ingestion, in particular due to their relative high molecular mass or the lack of specific transport systems or both; c) their rapid excretion through liver and kideneys; and d) their undesired effects caused by interaction of the conformationally flexible peptides with various receptors.