New antagonists of bombesin/gastrin-releasing peptide with C-terminal Leu (CH2N)Tac-NH2

H. Reile, Renzhi Cai, P. Armatis, A. V. Schally

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Several new pseudononapeptide bombesin/GRP analogs containing C-terminal Leuψ(CH2N)Tac-NH2 with variations at the N-terminus, corresponding to position 6 of bombesin, have been synthesized in order to develop more potent Bn antagonists for the hormonal therapy of cancers. The biological activities of the new compounds were evaluated in vitro by investigating their ability to inhibit the binding of [125I-Tyr4]Bn and to suppress the GRP(14-27)-stimulated DNA synthesis in quiescent Swiss 3T3 cells. All compounds investigated inhibited the binding of [125I-Tyr4]Bn, suppressed the GRP(14-27)-induced proliferation of Swiss 3T3 cells in a dose-dependent manner and proved to act as Bn antagonists without agonistic activity. Two of the newly synthesized pseudononapeptides [Hca6, Leu13ψ(CH2N)-Tac14]Bn(6-14) (RC-3940-II) and [D-Nal6, Leu13ψ (CH2N)Tac14]Bn(6-14) (RC-3965-II) exhibited higher binding affinities to Swiss 3T3 cells than the Bn/GRP antagonist RC-3095 and the recently developed compound [D-Phe6, Leu13ψ(CH2N) Tac14]Bn(6-14) (RC-3950-II). RC-3940-II caused 50% inhibition of the specific binding of [125I-Tyr4]Bn to Swiss 3T3 cells at concentrations less than 1 pM and suppressed by 50% the GRP(14-27)-induced proliferation of Swiss 3T3 cells at doses one order of magnitude lower than RC-3095. This study demonstrates the importance of the nature of the N-terminus in addition to the C-terminal Leuψ(CH2N)Tac-NH. The elimination of the free amino group in the aromatic residue in position 6 appears to increase the antagonistic activity. These findings suggest the merit of further investigations of this class of Bn/GRP antagonists for their antitumor activities in various cancers.

Original languageEnglish (US)
Pages (from-to)749-754
Number of pages6
JournalInternational journal of oncology
Issue number4
StatePublished - Jan 1 1995
Externally publishedYes


  • Bombesin
  • Gastrin-releasing peptide
  • Swiss 3T3 cells bombesin antagonist

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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