Page - (000239) - in Biomedical Chemistry: Current Trends and Developments

govern their three-dimensional configuration [e.g. conformation (χ), polar angle (θ), and overall stereo geometry]. Changes in composition, sequence, and intramolecular bonds may profoundly affect the structure-activity relationships of antimicrobial peptides in solution, upon binding to target membranes, or during conformational phase transition to activated states. Therefore, optimal antimicrobial peptide efficacy lies in the relevant coordination of these relationships (shaded area) as they relate to microbial target versus host cells in a particular context of infection (adapted from Yeaman & Yount, 2003). In current practice, it is known that AMPs not only target cell membranes but may have intracellular targets. The AMP buforin II kills E. coli without lysis of the cell membrane. Buforin II penetrates the cell membrane, accumulates inside the bacterial cell and binds to the DNA and RNA, which leads to cell death by inhibiting cellular functions (Park, 1998). Pleurocidin inhibits DNA and protein synthesis in E. coli without damaging the cytoplasmic membrane (Patrzykat, 2002). Other AMPs inhibit enzymatic activities inside the target cell such as phyrrhocoricin, apidaecin, and drosocin, which interact with the E. coli heat shock protein DnaK and inhibit protein folding (Kragol, 2001). Some AMPs are capable of inducing apoptotic cell death, including the breakdown of mitochondrial membrane potential and activation of caspase 3-like activity, such as in Leishmania (Kulkarni, 2006). AMPs may have different target sites and act in more than one mechanism to kill the same species, and different AMPs may act synergistically (Fieck, 2010). According Boman, AMPs can be classified into three groups: a) linear, often α-helical peptides free of cysteine residues; b) peptides containing disulfide bridges, giving peptides a β-sheet structure; and c) peptides with an overrepresentation in certain amino acids, such as proline, arginine, tryptophan, or histidine (Boman, 2003). 3.1.3.1.2 α-Helical Peptides without Cys Residues Cecropin-AMP families share a similar structure containing two α-helical domains linked by a flexible region, and the different cecropins from different organisms vary in their range of antimicrobial activity. The antibacterial activity of insect cecropins is based on the pore formation in bacterial membranes (Ekengen & Hultmark, 1999; Tanaka, 2008). A