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

ABSTRACT: Antiproliferative factor (APF), a sialylated 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.

SUBMITTER: Kaczmarek P 

PROVIDER: S-EPMC4007904 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other