NDLI: Structure-function analyses involving palindromic analogs of tritrypticin suggest autonomy of anti-endotoxin and antibacterial activities.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nagpal, Sushma Khan, Tarique Kaur, Kanwal J. Sarkar, Pampi Salunke, Dinakar M.
Description	Country affiliation: India Author Affiliation: Kaur KJ ( National Institute of Immunology, New Delhi 110067, India.)
Abstract	Neutralization of invading pathogens by gene-encoded peptide antibiotics has been suggested to manifest in a variety of different modes. Some of these modes require internalization of the peptide through a pathway that involves LPS-mediated uptake of the peptide antibiotics. Many proline/tryptophan-rich cationic peptides for which this mode has been invoked do, indeed, show LPS (endotoxin) binding. If the mechanism of antibiotic action involves the LPS-mediated pathway, a positive correlation ought to manifest between the binding to LPS, its neutralization, and the bacterial killing. No such correlation was evident based on our studies involving minimal active analogs of tritrypticin. The anti-endotoxin activities of these analogs appear not to relate directly to their antibiotic potential. The two palindromic analogs of tritrypticin, NT7 (RRFPWWW) and CT7 (WWWPFRR), showed comparable antibacterial activities. However, while NT7 exhibited anti-endotoxin activity, CT7 did not. The LPS binding of two tritrypticin analogs correlated with their corresponding structures, but the antibacterial activities did not. Further structure-function analysis indicated specific structural implications of the antibacterial activity at the molecular level. Studies involving designed analogs of NT7 incorporating either rigid or flexible linkers between the specifically distanced hydrophobic and cationic clusters modulate the LPS binding. On the other hand, not knowing the target receptor for antibacterial activity is a drawback since the precise epitope for antibacterial activity is not definable. It is apparent that the anti-endotoxin and antibacterial activities represent two independent functions of tritrypticin, consistent with the emerging multifunctionality in the nature of cathelicidins.
ISSN	09618368
e-ISSN	1469896X
DOI	10.1110/ps.073145008
Journal	Protein Science
Issue Number	3
Volume Number	17
Language	English
Publisher	Wiley-Blackwell (on behalf of The Protein Society)
Publisher Date	2008-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anti-bacterial Agents Chemistry Pharmacology Lipopolysaccharides Antagonists & Inhibitors Oligopeptides Metabolism B-lymphocytes Drug Effects Cell Proliferation Nitric Oxide Peptides Polymyxin B Structure-activity Relationship Research Support, Non-u.s. Gov't Discipline Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry

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