Elsevier

Life Sciences

Volume 45, Issue 17, 1989, Pages 1521-1527
Life Sciences

NisobutyrylHisTrpAlaValDAlaHisLeuNHMe (ICI 226140) a potent in vivo antagonist analogue of bombesin/gastrin releasing peptide (BN/GRP) derived from the c-terminal sequence lacking the final methionine residue

https://doi.org/10.1016/0024-3205(89)90417-7Get rights and content

Abstract

The GRP receptor mediated growth response in Swiss 3T3 cells has been used to identify BN/GRP antagonists. Analysis of bombesin antagonism by substance P analogues and by truncated GRP analogues revealed that deletion of the C-terminal methionine residue was important for antagonism. Des-Met analogues showing potent antagonist activity in the in vitro 3T3 system (IC50 ∼2nM) were synthesized. Further structural modification of these peptides led to the identification of (CH3)2CHCOHisTrpAlaValDAlaHisLeuNHCH3 (ICI 216140) which reduced bombesin-stimulated rat pancreatic amylase secretion to basal levels when administered subcutaneously at 2.0 mg per kg.

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