Recent research advances of Pro-rich antimicrobial peptides / 中国药理学通报

Pro-rich antimicrobial peptides are a group of linear peptides isolated from animals. These peptides have antibacterial activities and play an important role in innate immunity. Pro-rich antimicrobial peptides are devided into two classes:Pro-rich antimicrobial peptides from mammals and Pro-rich antimicrobial peptides from insects and other invertebrates.Members of Pro-rich antimicrobial peptides are all characterised by a high content of proline residues and predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism,at variance with the majority of the known antimicrobial peptides. Evidence is accumulating that the Pro-rich peptides enter the cells without membrane lysis and,once in the cytoplasm,bind to,and inhibit the activity of DnaK protein that is essential to bacterial growth,thereby causing responsive bacteria death. This mode of action makes these peptides suitable for drug development efforts. As one of the best characterized Pro-rich peptides,PR-39 plays an important role in a number of biological processes. It has been found that PR-39 can induce the syndecan expression in mesenchymal cells, inhibit the NADPH oxidase activity of neutrophils and block the degradation of 1?B? and HIF-1?. These findings show that PR-39 can provide novel means in the control of inflammation, wound repair, ischemia-reperfusion injury,and angiogenesis for therapeutic purposes.

Promising drugs to treat Alzheimers disease——?-secretase inhibitors / 中国药理学通报

Mutations in presenilins caused most of the autosomal dominant familial forms of Alzheimers disease by altering ? secretase activity. The ? secretase is a large multiprotein complex including presenilin heterodimers,nicastrin,PEN 2 and additional unidentified components.? secretase cleaves beta amyloid precursor protein,Notch,E cadherin,ErbB 4 receptor tyrosine kinase and other membrane proteins.The development of various ? secretase inhibitors not only provides a tool for investigating the structure, function and mechanism of ? secretase,but also presents a therapeutic strategy to slow progression of Alzheimers disease pathology. Threre are various classes of ? secretase inhibitors: compounds containing a difluoro ketone or a difluoro alcohol group, (hydroxyethy) urea peptidomimetics,compounds possessing a hydroxyethylene dipeptide isostere, short helical peptides, non peptidic inhibitors derived from 4 chloro isocoumarin synthon, compounds containing alanyl moiety.Among these species of ? secretase inhibitors,those which selectively affect Abeta production are especially the most promising drugs to treat Alzheimers disease.