Diprotin A
(Synonyms: 抑二肽素A,Ile-Pro-Ile) 目录号 : GC45436
A tripeptide inhibitor of DPP-4
Cas No.:90614-48-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Diprotin A is a tripeptide inhibitor of dipeptidyl peptidase 4 (DPP-4; IC50 = 1.1 μg/ml).1 It inhibits degradation of glucagon-like peptide 1 in culture with insulin-secreting BRIN-BD11 rat pancreatic β-cells when used at a concentration of 25 μM.2 Diprotin A (5 mg/ml) pre-incubation enhances chemotaxis of murine embryonic stem cells towards stromal cell-derived factor-1 (SDF-1/CXCL12) in vitro.3 Pre-incubation of CD34+ human umbilical cord blood cells with diprotin A (5 mM) prior to injection increases engraftment in NOD/SCID recipient mice.4
References
1. Umezawa, H., Aoyagi, T., Ogawa, K., et al. Diprotins A and B, inhibitors of dipeptidyl aminopeptidase IV, produced by bacteria. J. Antibiot. (Tokyo) 37(4), 422-425 (1984).
2. Green, B.D., Liu, H.K., McCluskey, J.T., et al. Function of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1. Diabetes Obes. Metab. 7(5), 563-569 (2005).
3. Guo, Y., Hangoc, G., Bian, H., et al. SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells. Stem Cells 23(9), 1324-1332 (2005).
4. Campbell, T.B., Hangoc, G., Liu, Y., et al. Inhibition of CD26 in human cord blood CD34+ cells enhances their engraftment of nonobese diabetic/severe combined immunodeficiency mice. Stem Cells Dev. 16(3), 347-354 (2007).
| Cas No. | 90614-48-5 | SDF | |
| 别名 | 抑二肽素A,Ile-Pro-Ile | ||
| Canonical SMILES | O=C([C@@H](N)[C@@H](C)CC)N1CCC[C@H]1C(N[C@H](C(O)=O)[C@@H](C)CC)=O | ||
| 分子式 | C17H31N3O4 | 分子量 | 341.5 |
| 溶解度 | DMF: 33 mg/ml,DMSO: 25 mg/ml,Ethanol: 10 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9283 mL | 14.6413 mL | 29.2826 mL |
| 5 mM | 0.5857 mL | 2.9283 mL | 5.8565 mL |
| 10 mM | 0.2928 mL | 1.4641 mL | 2.9283 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Diprotin A TFA Exerts Neurovascular Protection in Ischemic Cerebral Stroke
Front Neurosci 2022 May 9;16:861059.PMID:35615279DOI:10.3389/fnins.2022.861059.
Background: It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved β-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice. Methods: C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 μg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area. Results: Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability. Conclusion: Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced β-catenin cleavage to protect blood vessels.
Diprotin A, an inhibitor of dipeptidyl aminopeptidase IV(EC 3.4.14.5) produces naloxone-reversible analgesia in rats
Life Sci 1999;64(2):145-52.PMID:10069492DOI:10.1016/s0024-3205(98)00544-x.
The dipeptidyl aminopeptidase IV (DP IV) inhibitor Diprotin A produces a full, dose-dependent, short-lasting and naloxone-reversible analgesia in the rat tail-flick test when given intracerebroventricularly, with an ED50 of 295 nmol/rat but it has no direct opioid agonist activity in the longitudinal muscle strip of guinea-pig ileum bioassay. Two of the potential DP IV substrates, morphiceptin and endomorphin 1, identified recently in bovine brain were also analgesic given by similar route. The action of endomorphin 1 was more potent (ED50 = 7.9 nmol/rat) and slightly but significantly more sustained than that of Diprotin A. Diprotin A neither potentiated nor prolonged the effect of a marginally analgesic dose of endomorphin 1. The distinct time course and the lack of potentiation indicate that in the analgesic effect of Diprotin A in rats the protection of a brain Tyr-Pro-peptide other than endomorphin 1 is involved.
Are Diprotin A (Ile-Pro-Ile) and diprotin B (Val-Pro-Leu) inhibitors or substrates of dipeptidyl peptidase IV?
Biochim Biophys Acta 1991 Jan 29;1076(2):314-6.PMID:1671823DOI:10.1016/0167-4838(91)90284-7.
Dipeptidyl peptidase IV preferably hydrolyzes peptides and proteins with a penultimate proline residue. Umezawa and co-workers (Umezawa et al. (1984) J. Antibiotics 37, 422-425) reported that Diprotin A (Ile-Pro-Ile) and diprotin B (Val-Pro-Leu) are inhibitors for dipeptidyl peptidase IV. We could show that both compounds as well as other tripeptides with a penultimate proline residue are substrates for dipeptidyl peptidase IV. An apparent competitive inhibition by those compounds is a kinetic artifact due to the substrate-like structure of such tripeptides.
Dipeptidyl Peptidase 4 Inhibitors Diprotin A and Sitagliptin Administered on Weeks 2-3 of Postnatal Development Modulate Monoamine Metabolism in the Striatum of Adult Rats
Bull Exp Biol Med 2017 Jun;163(2):190-194.PMID:28726205DOI:10.1007/s10517-017-3763-5.
The levels of monoamines and their metabolites in brain structures of adult (3-month-old) rats with emotional and motivational disorders induced by inhibitors of dipeptidyl peptidase 4 (DPP-4; EC 3.4.14.5) Diprotin A and sitagliptin on weeks 2-3 of postnatal development (postnatal days 5-18) were studied by HPLC with electrochemical detection. A significant decrease in the level of serotonin metabolite, 5-hydroxyindoleacetic acid, and a pronounced tendency towards reduced serotonin level were detected in the striatum of rats in both study groups. In adult rats treated with Diprotin A during the neonatal period, a tendency towards activation of dopamine metabolism was observed (judging from DOPAC/DA ratio). The levels of monoamines and their metabolites in the frontal cortex, hypothalamus, and amygdala remained unchanged. The findings suggest that administration of DPP-4 inhibitors during the neonatal period induces long-term dysfunction of the serotonergic and dopaminergic systems of the brain.
Diprotin A infusion into nonobese diabetic/severe combined immunodeficiency mice markedly enhances engraftment of human mobilized CD34+ peripheral blood cells
Stem Cells Dev 2007 Jun;16(3):361-70.PMID:17610366DOI:10.1089/scd.2007.9997.
Hematopoietic stem cell (HSC) graft cell dose impacts significantly on allogeneic transplant. Similarly, HSC gene therapy outcome is affected by loss of repopulating cells during culture required for ex vivo retrovirus transduction. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play a central role in marrow trafficking of HSCs, and maneuvers that enhance CXCR4 activation might positively impact outcome in settings of limiting graft dose. CD26/dipeptidyl peptidase IV (DPP-IV) is an ectoenzyme protease that cleaves SDF-1, thus reducing CXCR4 activation. We show that injection of irradiated nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with >or=2 micromol Diprotin A (a tripeptide specific inhibitor of CD26 protease activity) at the time of transplant of human granulocyte colony-stimulating factor (G-CSF) mobilized CD34(+) peripheral blood cells (CD34(+) PBCs) results in a >3.4-fold enhancement of engraftment of human cells. We also show that CD26 on residual stromal cells in the irradiated recipient marrow milieu, and not any CD26 activity in the human CD34(+) PBC graft itself, plays the critical role in regulating receptivity of this environment for the incoming graft. Human marrow stromal cells also express CD26, raising the possibility that Diprotin A treatment could significantly enhance engraftment of HSCs in humans in settings of limiting graft dose just as we observed in the NOD/SCID mouse human xenograft model.