Novel C-terminal gastrin antagonists

摘要: A series of derivatives the biologically active C-terminus gastrin was synthesized to study structural activity molecule and also determine smallest highest affinity inhibitor gastrin. Earlier work speculated that a peptide resistant dipeptidase contained in receptor would be an effective antagonist. Methods: Five dogs with both chronic gastric fistulae Heidenhein pouches were used. After 18 hour fast, juice collected from fistula pouch over 200 minutes at 10 minute intervals. MMC (Migrating Motor Complex) monitored by small balloon antrum. Collections initiated beginning phase I obtained under 3 conditions: Control, pentagastrin infusion (0.5 μg/Kg/h, i.v.) pentagastrin+peptide (Indole propionic acid [IPA]- Leu-Asp-Phenethyl amine [PEA], Boc-Trp-Leu-βAla, IPA-Leu-βAla, or Boc-Trp-Leu-Asp-methyl meta Aminobenzoic {mABAOMe] 20 pmol/kg/h for 70 min.). Pentagastrin started immediately before next peak MMC. Peptides infused 60 after starting infusion. Results: All four peptides inhibited stimulated secretion causing it approach control level. ______________________________________ Inhibition (Δ meq/kg) Gastric Fistula Pouch______________________________________IPA--Leu--Asp--PEA ↓303 ± 120* ↓18 11*Boc--Trp--Leu-βAla ↓618 168** ↓35 8**IPA--Leu-βAla ↓562 249* ↓34 12*Boc--Trp--Leu--Asp- ↓446 172** ↓40 16**mABAOMe______________________________________ (*p < 0.05 **p 0.01, mean s.e.) It is concluded even di-and tripeptide C-terminal fragment varied resistance hydrolysis can exhibit antagonist secretion.