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| 5mg |
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| Targets |
CCK-B receptor (cholecystokinin B/gastrin receptor) [4]
(Leu15)-Gastrin I (human) acts through G protein-coupled receptors known as cholecystokinin (CCK) or CCK-B receptors (CCK-BR). It is a potent agonist at the CCK-B receptor, which is primarily responsible for mediating the effects of gastrin on gastric acid secretion. By binding to and activating this receptor, the peptide triggers downstream signaling cascades that lead to the stimulation of acid production from parietal cells. |
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| ln Vitro |
In receptor autoradiography, (Leu15)-Gastrin I (human) labeled with iodine-125 showed high-density specific binding to CCK-B receptors in the midglandular region of human gastric fundic mucosa, correlating with parietal cell distribution. Binding was displaceable by unlabeled gastrin and sulfated CCK-8. No binding was detected in human antral mucosa. A low density of CCK-B receptors was also identified in the circular muscle layer of the fundus [4].
In rat gastric fundus, (Leu15)-Gastrin I (human) labeled the whole mucosa with lower intensity in the midglandular region [4]. In vitro, (Leu15)-Gastrin I (human) exhibits bioactivity similar to that of natural human gastrin-17. It binds to and activates the CCK-B receptor, a G-protein-coupled receptor. This activation triggers downstream signaling cascades involving phospholipase C, protein kinase C, and calcium mobilization. The peptide regulates the binding of cholecystokinin to the mucosal membrane, confirming its role in modulating gastrointestinal function through its receptor interactions. |
| ln Vivo |
In vivo, (Leu15)-Gastrin I (human) plays a crucial role in stimulating gastric acid secretion from parietal cells. It is involved in the regulation of mucosal growth and gastrointestinal function. The peptide's effects are mediated through the CCK-B receptor, which is expressed in the stomach and other tissues. Its activity in vivo is consistent with the known physiological roles of gastrin, making it a valuable tool for studying gastric physiology and related disorders.
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| Enzyme Assay |
Receptor autoradiography procedure for CCK-B/gastrin receptors using (Leu15)-Gastrin I (human): Cryostat sections (10-20 μm) of human gastric tissues were preincubated in 50 mmol/L Tris-HCl (pH 7.4) with 130 mmol/L NaCl, 4.7 mmol/L KCl, 5 mmol/L MgCl, 1 mmol/L EGTA, and 0.5% bovine serum albumin for 30 min at 25°C. Sections were then incubated with 55 pmol/L (Leu15)-Gastrin I (human) labeled with iodine-125 (2000 Ci/mmol) in the same buffer without bovine serum albumin, supplemented with 0.025% bacitracin, 1 mmol/L dithiothreitol, 2 μg/mL chymostatin, and 4 μg/mL leupeptin (pH 6.5) for 150 min at room temperature. Non-specific binding was determined with 100 nmol/L unlabeled gastrin. After incubation, slides were washed 6×15 min in ice-cold preincubation buffer (pH 7.4), rinsed twice in ice-cold distilled water, dried under cold air, and exposed to Hyperfilm for 1-7 days. Autoradiograms were quantified using computer-assisted image processing with iodinated tissue standards [4].
In vitro receptor binding assays for (Leu15)-Gastrin I (human) are performed to determine its affinity for the CCK-B receptor. Standard protocols involve competitive binding experiments using membrane preparations from cells expressing the receptor. Radiolabeled gastrin or a specific CCK-B antagonist is used as a tracer. Increasing concentrations of the peptide are incubated with the receptor membranes, and the displacement of the tracer is measured. The peptide's ability to regulate the binding of cholecystokinin to the mucosal membrane is a key endpoint in these assays. |
| Cell Assay |
In vitro cellular assays for (Leu15)-Gastrin I (human) are conducted using cell lines that express the CCK-B receptor, such as gastric or pancreatic cells. Cells are treated with the peptide, and receptor activation is measured by quantifying downstream signaling events, such as calcium mobilization or activation of protein kinase C. The peptide's ability to stimulate acid secretion can be assessed in parietal cell cultures. These assays confirm its functional activity as a CCK-B receptor agonist.
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| Animal Protocol |
In vivo animal studies for (Leu15)-Gastrin I (human) typically involve administering the peptide to rodents and measuring its effect on gastric acid secretion. A common protocol includes cannulation of the stomach to collect gastric juice, followed by administration of the peptide and measurement of acid output. The peptide's effects on mucosal growth can be assessed by histological analysis of the gastric mucosa after repeated dosing. These studies are used to investigate the physiological roles of gastrin and the potential of its analogues.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for (Leu15)-Gastrin I (human) are not detailed in standard references. As a peptide, it is expected to be rapidly degraded by proteases in the gastrointestinal tract and systemic circulation. Its stability is improved compared to the native peptide due to the leucine substitution. However, its bioavailability is likely limited, and its effects are primarily local in the gastrointestinal tract, where it is administered or endogenously released.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for (Leu15)-Gastrin I (human) are not typically reported, as it is a research peptide. Its toxicological profile is expected to be related to its pharmacological effects on gastric acid secretion and mucosal growth. High doses could potentially lead to hypergastrinemia, which is associated with gastric mucosal hypertrophy and, in chronic cases, an increased risk of gastric carcinoids. Standard toxicity studies would be required for any therapeutic development.
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| References | |
| Additional Infomation |
(Leu15)-Gastrin I (human) (also called Leu15-little gastrin or HG 17) was synthesized by solid-phase methods using 2-chlorotrityl resin and Fmoc/tBu strategy. The protected form (4b) was cleaved from resin with acetic acid/trifluoroethanol/dichloromethane (1:2:7 or 2:2:6) for 30 min at room temperature, giving 99% yield and >95% purity by HPLC. Full deprotection with TFA/water (95:5) or TFA/anisole (7:3) yielded free peptide (4c) in 63-64% after HPLC purification; structure confirmed by FAB-MS (m/z 2081 for MH+) [3]. In another study, crude protected (Leu15)-Gastrin I (human) (15a) was obtained in 99% yield using 2-chlorotrityl chloride resin, and free peptide (16) in 92% yield with 90% purity [1]. The compound was used as a radioligand for CCK receptor mapping in human stomach [4].
(Leu15)-Gastrin I (human) is a synthetic analogue of human gastrin-17 with a leucine substitution at position 15. It acts as a potent agonist at the CCK-B receptor, stimulating gastric acid secretion and regulating mucosal growth. The peptide triggers downstream signaling pathways involving phospholipase C, protein kinase C, and calcium mobilization. Its increased stability compared to the native peptide makes it a useful tool for studying gastrointestinal physiology. It is not an approved drug but is used in research. |
| Molecular Formula |
C98H126N20O31
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|---|---|
| Molecular Weight |
2080.16000
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| Exact Mass |
2078.89
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| CAS # |
39024-57-2
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| PubChem CID |
16170068
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| Appearance |
White to off-white solid powder
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| LogP |
3.656
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| Hydrogen Bond Donor Count |
26
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| Hydrogen Bond Acceptor Count |
31
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| Rotatable Bond Count |
61
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| Heavy Atom Count |
149
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| Complexity |
4740
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| Defined Atom Stereocenter Count |
15
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| SMILES |
C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)NCC(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC4=CC=CC=C4)C(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@@H]7CCCN7C(=O)CNC(=O)[C@@H]8CCC(=O)N8
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| InChi Key |
CMVMLPDUAGUTOC-FPBFVHJESA-N
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| InChi Code |
InChI=1S/C98H126N20O31/c1-49(2)38-68(115-96(147)72(43-55-46-101-60-19-12-10-17-58(55)60)117-98(149)74-20-13-37-118(74)77(122)48-103-86(137)61-25-31-75(120)105-61)93(144)111-66(30-36-82(131)132)92(143)110-65(29-35-81(129)130)91(142)109-64(28-34-80(127)128)90(141)108-63(27-33-79(125)126)89(140)107-62(26-32-78(123)124)88(139)104-51(5)85(136)113-70(41-53-21-23-56(119)24-22-53)87(138)102-47-76(121)106-71(42-54-45-100-59-18-11-9-16-57(54)59)95(146)114-69(39-50(3)4)94(145)116-73(44-83(133)134)97(148)112-67(84(99)135)40-52-14-7-6-8-15-52/h6-12,14-19,21-24,45-46,49-51,61-74,100-101,119H,13,20,25-44,47-48H2,1-5H3,(H2,99,135)(H,102,138)(H,103,137)(H,104,139)(H,105,120)(H,106,121)(H,107,140)(H,108,141)(H,109,142)(H,110,143)(H,111,144)(H,112,148)(H,113,136)(H,114,146)(H,115,147)(H,116,145)(H,117,149)(H,123,124)(H,125,126)(H,127,128)(H,129,130)(H,131,132)(H,133,134)/t51-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,74-/m0/s1
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| Chemical Name |
(4S)-5-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[(2S)-1-[2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]-5-oxopentanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~10.53 mg/mL (~5.06 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.4807 mL | 2.4037 mL | 4.8073 mL | |
| 5 mM | 0.0961 mL | 0.4807 mL | 0.9615 mL | |
| 10 mM | 0.0481 mL | 0.2404 mL | 0.4807 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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