Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aspartic acid residue at the penultimate position is known to be essential for the hormonal activity of CCK and gastrin on gastric acid secretion. This residue was successively replaced by beta-aspartic acid, beta-alanine, and glutamic acid in the C-terminal heptapeptide of CCK 27-33. The analogues obtained were tested on rat gastric acid secretion and for recognition by gastrin receptors. The replacement by beta-aspartic or beta-alanine decreased gastric secretion and gastrin receptor recognition. In contrast, replacement by glutamic acid affected these two parameters less. The nature of the N-blocking group (Boc or Z) also influenced these activities, Boc derivatives being more potent than Z derivatives. The results were compared to those previously obtained on pancreatic secretion and on stimulation of gall bladder contraction where the modifications were found capable of differentiating between cholecystokinin, pancreozymin and gastrin activities.
 ...
PMID:The role of the Asp-32 residue of cholecystokinin in gastric acid secretion and gastrin receptor recognition. 630 19

The rate and extent of membrane fusion is markedly sensitive to membrane interfacial properties. Lipopeptides with hydrophilic peptide moieties will insert into membranes, leaving the peptide portion at the membrane-water interface. In this work, we have used a lipopeptide composed of the peptide [Nle15]-gastrin-(2-17)-amide covalently linked to 1,2-diacyl-3-mercaptoglycerol-N(alpha)-maleoyl-beta-alanine to give DM-gastrin or DP-gastrin having 14 or 16 carbon atom acyl chains, respectively. The fluorescence emission from the two Trp residues of these lipopeptides exhibited little or no blue shift upon addition of liposomes of egg-phosphatidylethanolamine containing 5 mol% G(D1a). Iodide quenching of DP-gastrin fluorescence was also independent of lipid. These results indicate that the peptide moiety is exposed to the aqueous environment even though the lipopeptide is firmly anchored to the membrane. Both DM and DP-gastrin markedly raise the bilayer to hexagonal phase transition temperature of dipalmitoleoyl phosphatidylethanolamine. However, DM-E5 lowers this phase transition temperature. These lipopeptides have effects on the overall fusion of Sendai virus to liposomes in accord with their opposite effects on lipid curvature. The lipogastrins are potent inhibitors of viral fusion, while DM-E5 slightly promotes this process. Truncated forms of DM-gastrin are also inhibitory to viral fusion, but are less inhibitory than the full lipopeptide. Analysis of the fusion kinetics shows that DP-gastrin causes a reduction in the final extent of fusion and a marked lowering of the fusion rate constant. Binding of Sendai virus to the ganglioside receptor-containing liposomes was not affected. Consideration of the various contributions to the mechanism of inhibition of viral fusion suggests that effects of lipogastrin on membrane intrinsic monolayer curvature is of primary importance.
 ...
PMID:Lipogastrins as potent inhibitors of viral fusion. 927 Dec 68

Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and specificity. The GRPr is overexpressed on a variety of human cancer cells, including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to develop (99m)Tc-radiolabeled BBN analogues that maintain high specificity for the GRPr in vivo. A preselected synthetic sequence via solid-phase peptide synthesis (SPPS) was designed to produce N(3)S-BBN (N(3)S = dimethylglycyl-l-seryl-l-cysteinylglycinamide) conjugates with the following general structure: DMG-S-C-G-X-Q-W-A-V-G-H-L-M-(NH(2)), where the spacer group, X = 0 (no spacer), omega-NH(2)(CH(2))(2)COOH, omega-NH(2)(CH(2))(4)COOH, omega-NH(2)(CH(2))(7)COOH, or omega-NH(2)-(CH(2))(10)COOH. The new BBN constructs were purified by reversed phase-HPLC (RP-HPLC). Electrospray mass spectrometry (ES-MS) was used to characterize the nonmetalated BBN conjugates. Re(V)-BBN conjugates were prepared by the reaction of Re(V)gluconate with N(3)S-X-BBN[7-14]NH(2) (X = 0 carbons, beta-Ala (beta-alanine), 5-Ava (5-aminovaleric acid), 8-Aoc (8-aminooctanoic acid), and 11-Aun (11-aminoundecanoic acid)) with gentle heating. Re-N(3)S-5-Ava-BBN[7-14]NH(2) was also prepared by the reaction of [Re(V)dimethylglycyl-l-seryl-l-cysteinylglycinamide] with 5-Ava-BBN[7-14]NH(2). ES-MS was used to determine the molecular constitution of the new Re(V) conjugates. The (99m)Tc conjugates were prepared at the tracer level by each the prelabeling, post-conjugation and pre-conjugation, postlabeling approaches from the reaction of Na[(99m)TcO(4)] with excess SnCl(2), sodium gluconate, and corresponding ligand. The (99m)Tc and Re(V) conjugates behaved similarly under identical RP-HPLC conditions. In vitro and in vivo models demonstrated biological integrity of the new conjugates.
 ...
PMID:Radiochemical investigations of (99m)Tc-N(3)S-X-BBN[7-14]NH(2): an in vitro/in vivo structure-activity relationship study where X = 0-, 3-, 5-, 8-, and 11-carbon tethering moieties. 1252 98

The synthesis of the novel pentagastrin seco-CBI conjugate 3, which is based on the highly cytotoxic antitumor antibiotic (+)-duocarmycin SA (1), is reported. A key step in the synthesis is the palladium-catalyzed carbonylation of aryl bromide 7 to give the benzyl ester 16, which is transformed into the new seco-CBI derivative 21 bearing a carboxylic acid ester moiety. Subsequent transformation of 21 into an activated ester followed by the introduction of beta-alanine and tetragastrin led to the new pentagastrin drug 3 that contains a peptide moiety for targeting cancer cells expressing CCK-B/gastrin receptors.
 ...
PMID:Synthesis of a novel pentagastrin-drug conjugate for a targeted tumor therapy. 1821 80