My NCBISign In

Display Settings:

Format

Send to:

Choose Destination
    J Med Chem. 2010 Aug 12;53(15):5782-91.

    Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

    Nomme J, Renodon-Cornière A, Asanomi Y, Sakaguchi K, Stasiak AZ, Stasiak A, Norden B, Tran V, Takahashi M.

    Source

    UMR 6204 U-3B, Centre National de la Recherche Scientifique & Universite de Nantes, France.

    Abstract

    We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

    PMID:
    20684611
    [PubMed - indexed for MEDLINE]
    PMCID: PMC2917172
    Free PMC Article

    Images from this publication.See all images (8) Free text

    Figure 1
    Figure 5
    Figure 7
    Figure 3
    Figure 6
    Figure 8
    Figure 4
    Figure 2

    Publication Types, MeSH Terms, Substances

    Publication Types

    MeSH Terms

    Substances

    LinkOut - more resources

    Full Text Sources

    Medical

      Supplemental Content

      Click here to read Click here to read

      Related citations

      See reviews... See all...

      Cited by 1 PubMed Central article

      Related information

      • Related Citations
        Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
      • BioAssay
        PubChem BioAssay experiments on the biological activities of small molecules that cite the current articles. The depositors of BioAssay data provide these references.
      • Compound (MeSH Keyword)
        PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • References for this PMC Article
        Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
      • Substance (MeSH Keyword)
        PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Free in PMC
        Free full text articles in PMC
      • Cited in PMC
        Full-text articles in the PubMed Central Database that cite the current articles.

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      You are here: NCBI > Literature > PubMed
      Write to the Help Desk