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PDBsum entry 2igr
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De novo protein, lipid binding protein
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PDB id
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2igr
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References listed in PDB file
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Key reference
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Title
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Structure and function of a custom anticancer peptide, Cb1a.
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Authors
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J.M.Wu,
P.S.Jan,
H.C.Yu,
H.Y.Haung,
H.J.Fang,
Y.I.Chang,
J.W.Cheng,
H.M.Chen.
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Ref.
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Peptides, 2009,
30,
839-848.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Several natural antimicrobial peptides including cecropins, magainins and
melittins have been found to kill cancer cells. However, their efficacy may not
be adequate for their development as anticancer agents. In this study, we used a
natural antimicrobial peptide, cecropin B (CB), as a template to generate a
novel anticancer peptide. Cecropin B is an amphipathic and polycationic peptide
derived from the hemolymph of Hyalophora cecropia with well-known antimicrobial
and cytolytic properties. The signature pattern of cecropins is
W-x-(0,2)-[KDN]-x-{L}-K-[KRE]-[LI]-E-[RKN] (PROSITE: PS00268), and this
signature sequence is located at N-terminus of CB. CB1a was constructed by
repeating the N-terminal ten amino acids of CB three times and including a hinge
near C-terminus. The circular dichroism spectra showed that CB1a is unstructured
in aqueous solution, but adopt a helical conformation in membrane-like
environment. The solution structure of CB1a in a polar solvent was also studied
by NMR. CB1a formed a helix-hinge-helix in 20% HFIP solution, and it was found
the bent angle between two helical segments was induced ranging from 60 degrees
to 110 degrees . A heparin-binding motif is located in the central part of helix
1. Isothermal titration calorimetry reveals the association constant of CB1a
bound to low molecular weight heparin is 1.66 x 10(5)M(-1) at physiological
ionic strength at 25 degrees C. Binding of CB1a to heparin produces a large
conformational change toward a more structural state. CB1a demonstrated
promising activity against several cancer cells but low toxicity against
non-cancer cells. The IC(50) of CB1a on leukemia and stomach carcinoma cells
were in the range of 2-8-fold lower than those of CB. Besides, CB1a exhibited
low hemolytic activity against human red blood cells. Due to these properties,
CB1a has the potential to become a promising anticancer agent.
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