Bioactivity of analogs of the N-terminal region of gastrin-17

Jeffrey Copps, Shawn Ahmed, Richard F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Gastrin-17-Gly (G17-Gly) has been shown to bind to non-CCK nanomolar and micromolar affinity sites on DLD-1 and HT-29 human colonic carcinoma cells and to stimulate cellular proliferation. However, in previous studies, we showed that C-terminal truncation of the gastrin-17 (G17) to the G17 analog G17(1-12) and then to G17(1-6)-NH2 did not remove the ability to bind to DLD-1 cells or to activate proliferation. This implies that residues and/or structural motifs required for bioactivity at these receptors rest in the N-terminal region of G17. In this work, radioligand binding studies conducted with further C-terminally truncated analogs revealed that sequences as short as G17(1-4) still bind to a single receptor with micromolar affinity. Additionally, cell proliferation assays showed that G17(1-12) stimulates proliferation of DLD-1 cells, as of HT-29 cells, but the sequences shorter than G17(1-6)-NH2, including non-amidated G17(1-6), were incapable of stimulating proliferation. These observations indicate that the tetrapeptide pGlu-Gly-Pro-Trp is the minimum N-terminal sequence for binding to the probable growth-promoting site on DLD-1 cells. Since analogs shorter than G17(1-6) are able to bind the receptor, these peptides may be of use for developing selective antagonists.

Original languageEnglish (US)
Pages (from-to)2263-2267
Number of pages5
JournalPeptides
Volume30
Issue number12
DOIs
StatePublished - Dec 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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