2p7r: Difference between revisions

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[[Image:2p7r.jpg|left|200px]]
{{Seed}}
[[Image:2p7r.png|left|200px]]


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{{STRUCTURE_2p7r|  PDB=2p7r  |  SCENE=  }}  
{{STRUCTURE_2p7r|  PDB=2p7r  |  SCENE=  }}  


'''Cyclic pentapeptide which inhibits Hantavirus'''
===Cyclic pentapeptide which inhibits Hantavirus===




==Overview==
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Hantavirus-induced diseases such as hantavirus cardiopulmonary syndrome and hemorrhagic fever with renal syndrome are a global health concern. Hantavirus cardiopulmonary syndrome caused by Sin Nombre virus lacks specific therapy and its high mortality makes Sin Nombre virus a potential bioweapon agent. Sin Nombre virus entry into susceptible cells requires expression of alpha(v)beta(3) integrin. We recently reported the sequence of a cyclic nonapeptide that inhibited Sin Nombre virus entry into Vero E6 cells at a level comparable to ReoPro, a Fab fragment of the anti-beta(3) antibody c7E3. Here, we refine the parental peptide, cyclo-[CPFVKTQLC], using alanine scanning and amino acid deletions, by optimizing for viral inhibition. The IC(50) of the resulting peptide, cyclo-[CPFVC], was 267 microM compared with 263 microM for the parental peptide. The solution structure of cyclo-[CPFVC] was determined by two-dimensional nuclear magnetic resonance spectroscopy, revealing the Phe ring in an extended conformation stacked against the Pro ring and containing a beta-turn encompassing Val-4 through Cys-1. As an initial step in identifying interactions between cyclo-[CPFVC] and its target cellular receptor, the refined peptide structure was docked into the ReoPro binding site of integrin beta(3). This structure will provide the basis for designing more potent peptidomimetic therapeutics to prevent Sin Nombre virus entry and treat hantavirus cardiopulmonary syndrome.
The line below this paragraph, {{ABSTRACT_PUBMED_17441904}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 17441904 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17441904}}


==About this Structure==
==About this Structure==
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P7R OCA].  
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P7R OCA].  


==Reference==
==Reference==
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[[Category: Biosynthetic protein]]
[[Category: Biosynthetic protein]]
[[Category: Cyclic pentapeptide]]
[[Category: Cyclic pentapeptide]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 12:33:52 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:05:51 2008''

Revision as of 03:05, 29 July 2008

File:2p7r.png

Template:STRUCTURE 2p7r

Cyclic pentapeptide which inhibits Hantavirus

Template:ABSTRACT PUBMED 17441904

About this Structure

Full experimental information is available from OCA.

Reference

Characterization and NMR solution structure of a novel cyclic pentapeptide inhibitor of pathogenic hantaviruses., Hall PR, Malone L, Sillerud LO, Ye C, Hjelle BL, Larson RS, Chem Biol Drug Des. 2007 Mar;69(3):180-90. PMID:17441904

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