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Structure-Activity Studies on Antiproliferative Factor (APF) Glycooctapeptide Derivatives

  1. Author:
    Kaczmarek, P.
    Tocci, G. M.
    Keay, S. K.
    Adams, K. M.
    Zhang, C. O.
    Koch, K. R.
    Grkovic, D.
    Guo, L.
    Michejda, C. J.
    Barchi, J. J.

  2. Author Address

    [Kaczmarek, Piotr; Adams, Kristie M.; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Frederick, MD 21702 USA. [Tocci, Gillian M.; Michejda, Christopher J.] NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Keay, Susan K.; Koch, Kristopher R.; Grkovic, David; Guo, Li] Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA. [Keay, Susan K.] Vet Adm Maryland Hlth Care Syst, Res Serv, Baltimore, MD 21201 USA. [Zhang, Chen-Ou] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.;Barchi, JJ, NCI, Biol Chem Lab, Mol Discovery Program, Frederick, MD 21702 USA.;barchi@helix.nih.gov
    1. Year: 2010
    2. Date: Nov
  2. Journal: Acs Medicinal Chemistry Letters
    1. 1
    2. 8
    3. Pages: 390-394
  4. Type of Article: Article
  5. ISSN: 1948-5875
  1. Abstract:

    Antiproliferative factor (APF) alsialylated glycopeptide secreted by explanted bladder epithelial cells from interstitial cystitis/painful bladder syndrome (IC/PBS) patients and its unsialylated analogue (as-APF) significantly decrease proliferation of bladder epithelial cells and/or certain carcinoma cell lines in vitro. We recently reported a structure-activity relationship profile for the peptide portion of as-APF and revealed that truncation of the C-terminal alanine did not significantly affect antiproliferative activity to better understand the structural basis for the maintenance of activity of this truncated eight amino acid as-APF. (as-APF8), we synthesized several amino acid-substituted derivatives and studied their ability to inhibit bladder epithelial cell proliferation in vitro as well as their solution conformations by CD and NMR spectroscopy. While single amino acid changes to as-APF8 often strongly reduced activity full potency was retained when the trivaline tail was replaced with three alanines. The Ala(6-8) derivative 9 is the simplest fully potent APF analogue synthesized to date.

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External Sources

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  2. DOI: 10.1021/ml100087a
  3. View record in Web of Science®
  4. WOS: 000284203100005

Library Notes

  1. Fiscal Year: FY2010-2011
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