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Báo cáo hóa học: " PEGylating a bacteriophage endolysin inhibits its bactericidal activity"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí hóa hoc quốc tế đề tài : PEGylating a bacteriophage endolysin inhibits its bactericidal activity | Resch et al. AMB Express 2011 1 29 http www.amb-express.eom content 1 1 29 o AMB Express a SpringerOpen Journal ORIGINAL Open Access PEGylating a bacteriophage endolysin inhibits its bactericidal activity Gregory Resch1 2 Philippe Moreillon2 and Vincent A Fischetti1 Abstract Bacteriophage endolysins lysins bind to a cell wall substrate and cleave peptidoglycan resulting in hypotonic lysis of the phage-infected bacteria. When purified lysins are added externally to Gram-positive bacteria they mediate rapid death by the same mechanism. For this reason novel therapeutic strategies have been developed using such enzybiotics. However like other proteins introduced into mammalian organisms they are quickly cleared from systemic circulation. PEGylation has been used successfully to increase the in vivo half-life of many biological molecules and was therefore applied to Cpl-1 a lysin specific for S. pneumoniae. Cysteine-specific PEGylation with either PEG 10K or 40K was achieved on Cpl-1 mutants each containing an additional cysteine residue at different locations To the best of our knowledge this is the first report of the PEGylation of bacteriophage lysin. Compared to the native enzyme none of the PEGylated conjugates retained significant in vitro anti-pneumococcal lytic activity that would have justified further in vivo studies. Since the anti-microbial activity of the mutant enzymes used in this study was not affected by the introduction of the cysteine residue our results implied that the presence of the PEG molecule was responsible for the inhibition. As most endolysins exhibit a similar modular structure we believe that our work emphasizes the inability to improve the in vivo half-life of this class of enzybiotics using a cysteine-specific PEGylation strategy. Keywords Bacteriophage S. pneumoniae Cpl-1 PEGylation Endolysin Enzybiotic Introduction Streptococcus pneumoniae is the first cause of otitis media and a common cause of sinusitis community-acquired pneumonia