These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Development of potent gastrin-releasing peptide antagonists having a D-Pro-psi(CH2NH)-Phe-NH2 C terminus.
    Author: Leban JJ, Kull FC, Landavazo A, Stockstill B, McDermed JD.
    Journal: Proc Natl Acad Sci U S A; 1993 Mar 01; 90(5):1922-6. PubMed ID: 8446610.
    Abstract:
    Gastrin-releasing peptide (GRP) is a 27-amino acid neuroendocrine hormone that may play a role in the pathophysiology of small cell lung carcinoma. GRP and bombesin, a structurally related peptide, stimulate the growth of some cultured cell types. C-terminal GRP peptide analogs were developed that inhibited 6 nM bombesin-induced [3H]thymidine incorporation into quiescent murine Swiss 3T3 cells, which routinely produced a 6-fold stimulation over the basal extent of incorporation. The peptides were also analyzed for their capacity to inhibit the binding of 50 pM 125I-labeled GRP to Swiss 3T3 cells. The combination of two chemical modifications, each antagonistic in itself, led to the creation of antagonists with orders of magnitude greater potency than either modification alone. (i) Antagonist analogs of the form -Leu26-psi(CH2NH)-Xaa27-NH2 [where Xaa is Leu, norleucine (Nle), or Phe; residues numbered after GRP], similar to those introduced by Coy and coworkers [for review, see Jensen, R. T. & Coy, D. H. (1991) Trends Pharmacol. Sci. 12, 13-19], were found to have nanomolar potencies. (ii) We found that an octapeptide C-terminal GRP analog having D-Pro adjacent to the C-terminal amino acid amide was antagonistic, with a potency of 40 nM. By combining both modifications, specific analogs were found with potencies > 1000-fold greater than our lead structure--[(4'-hydroxy)-3-phenylpropanoyl]-Pro-Arg-Gly-Asn-His-Tr p-Ala-Val - Gly-His-Leu-psi(CH2NH)-Nle-NH2--and greater than any antagonist previously reported. The analogs [(4'-hydroxy)-3-phenylpropanoyl]-His-Trp-Ala-Val-D-Ala-His-D-Pro- psi(CH2NH)-Phe-NH2 and 1-naphthoyl-His-Trp-Ala-Val-D-Ala-His-D-Pro-psi(CH2NH)-Phe-NH2 antagonized [3H]thymidine incorporation with IC50 values of approximately 0.3 nM and inhibited the binding of 125I-labeled GRP with IC50 values of approximately 1 pM. These peptides may be of use in the study of the physiology of GRP.
    [Abstract] [Full Text] [Related] [New Search]