Dipeptidyl peptidase Ⅲ在先天性白内障大鼠晶状体中的免疫活性变化

目的 观察 8、10、12、14周龄正常及先天性白内障大鼠晶状体中dipeptidylpep tidaseⅢ (DPPⅢ )的免疫活性变化 ,探讨其与白内障发病的关系。方法 分别于 8、10、12、14周龄鼠 ,摘取正常对照组以及先天性白内障大鼠晶状体 ,应用抗生物素蛋白 生物素 过氧化物酶复合体法 ,观察不同时期大鼠晶状体中DPPⅢ的免疫活性变化。结果 各周龄先天性白内障大鼠晶状体纤维部DPPⅢ的免疫活性明显高于正常对照组 ,特别是 12、14周白内障晶状体中DPPⅢ的免疫阳性产物扩展至晶状体核周部。结论 DPPⅢ在白内障大鼠晶状体中免疫活性增强 ,它有可能在白内障形成过程中参与晶状体蛋白的水解分化 ,从而促进白内障的形成。

Dipeptidyl peptidase Ⅳ(DPP Ⅳ):a novel emerging target for thetreatment of type 2 diabetes

The enzyme, dipeptidyl peptidase IV（DPP IV）, is a novel target for the treatment of type 2 diabetes. Dipeptidyl peptidase IV inhibition improves the impaired insulin secretion and decrease postprandial concentrations of glucagon by enhancing the incretin hormone levels lucagon-like peptide-1（GLP-1） and glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide（GIP）. Recently, DPP IV inhibitors have attracted more and more attention, several of which have entered pre-clinical and clinical trials, and one has received approval for use as an anti-diabetic agent. Among the DPP IV inhibitors, two leading agents（sitagliptin and vildagliptin） have been shown to be effective in reducing glycosylated hemoglobin（HbAlc） and fasting plasma glucose（FPG） in patients with type 2 diabetes. This review summarizes the evidence supporting DPP IV inhibitors as potential antidiabetic agents.

Anti-diabetic potential of Urena lobata leaf extract through inhibition of dipeptidyl peptidase IV activity

Objective: To evaluate the anti-diabetic potential of leaf extract from Urena lobata(U. lobata) through dipeptidyl peptidase IV(DPP-IV) inhibitory activity.Methods: U. lobata leaf was extracted in hot water and ethanol. The activity of DPPIV inhibitor was tested by in vitro study using gly-pro-p-nitroanilide as substrat of DPPIV and vildagliptin, as standard reference. A product of the reactions between gly-pro-pnitroanilide and DPP-IV, was observed by microplate readers with λ = 405 nm. All data were expressed as mean ± SD and the IC50 value was determined by non linear regression curve fit. Active substances in leaf extract of U. lobata was analyzed by liquid chromatography-mass spectrometry. DPP-IV inhibitory activity of active compounds was evaluated in silico using docking server. Results: The ethanolic extract of U. lobata showed stronger DPP-IV inhibitor activity than water extract with the IC50 values of 1 654.64 and 6 489.88 μg/mL, respectively. Vildagliptin, based on standard reference for DPP-IV inhibitor activity, has IC50 value of 57.44 μg/mL. Based on in silico analysis, mangiferin, stigmasterol and β-sitosterol in U. lobata extract have a strong inhibitory activity on DPP-IV. Conclusions: The results showed that DPP-IV inhibitory activity of U. lobata is related to its active compounds such as mangiferin, stigmasterol and β-sitosterol.

Regulation of dipeptidyl peptidase 8 and 9 expression in activated lymphocytes and injured liver

AIM:To investigate the expression of dipeptidyl peptidase(DPP) 8 and DPP9 in lymphocytes and various models of liver fibrosis.METHODS:DPP8 and DPP9 expression were measured in mouse splenic CD4 + T-cells,CD8 + T-cells and B-cells(B220 +),human lymphoma cell lines and mouse splenocytes stimulated with pokeweed mitogen(PWM) or lipopolysaccharide(LPS),and in dithiothreitol(DTT) and mitomycin-C treated Raji cells.DPP8 and DPP9 expression were measured in epidermal growth factor(EGF) treated Huh7 hepatoma cells,in fibrotic liver samples from mice treated with carbon tetrachloride(CCl 4) and from multidrug resistance gene 2(Mdr2 /Abcb4) gene knockout(gko) mice with biliary fibrosis,and in human end stage primary biliary cirrhosis(PBC).RESULTS:All three lymphocyte subsets expressed DPP8 and DPP9 mRNA.DPP8 and DPP9 expression were upregulated in both PWM and LPS stimulated mouse splenocytes and in both Jurkat T-and Raji B-cell lines.DPP8 and DPP9 were downregulated in DTT treated and upregulated in mitomycin-C treated Raji cells.DPP9transfected Raji cells exhibited more annexin V + cells and associated apoptosis.DPP8 and DPP9 mRNA were upregulated in CCl 4 induced fibrotic livers but not in the lymphocytes isolated from such livers,while DPP9 was upregulated in EGF stimulated Huh7 cells.In contrast,intrahepatic DPP8 and DPP9 mRNA expression levels were low in the Mdr2 gko mouse and in human PBC compared to non-diseased livers.CONCLUSION:These expression patterns point to biological roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis.

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment

The last few years important changes have occurred in the field of diabetes treatment.The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors,while individualization of glycemic target is suggested.Furthermore,regulatory authorities now require evidence of cardiovascular(CV)safety in order to approve new antidiabetic agents.The most novel drug classes,i.e.,sodium-glucose transporter 2 inhibitors(SGLT2-i)and some glucagon-like peptide-1 receptor agonists(GLP-1 RA),have been demonstrated to reduce major adverse CV events and,thus,have a prominent position in the therapeutic algorithm of hyperglycemia.In this context,the role of previously used hypoglycemic agents,including dipeptidyl peptidase 4(DPP-4)inhibitors,has been modified.DPP-4 inhibitors have a favorable safety profile,do not cause hypoglycemia or weight gain and do not require dose uptitration.Furthermore,they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes.Still,though,they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA.Overall,DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.

Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes

The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.

Identification and dipeptidyl peptidase Ⅳ(DPP-Ⅳ) inhibitory activity verification of peptides from mouse lymphocytes

The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.

Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leukoplakia

AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.

Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4

Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research.Here,we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by a-naphthyl isothiocyanate(ANIT).We found that carboxylesterase 1(CES1),as an intrahepatic marker,and dipeptidyl peptidase 4(DPP-IV),as an extrahepatic marker,can reflect the different pathophysiologies of liver injury.Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state,respectively.While the levels of the conventional serological biomarkers alkaline phosphatase(ALP),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were all concomitantly elevated in serum and tissues after ANIT-induced injury,the levels of bile acids decreased in bile,increased in serum,and ascended in intrahepatic tissue.Although the level of γ-glutamyl transpeptidase(γ-GT)changed in an opposite direction,the duration was much shorter than that of CES1 and was quickly restored to normal levels.Therefore,among the abovementioned biomarkers,only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation.CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid(UDCA;single component)and Qing Fei Pai Du Decoction(QFPDD;multicomponent).We found that both QFPDD and UDCA attenuated ANIT-induced liver damage.UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and antiinflammatory effects than QFPDD,whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage.Our data highlights the potential of the combined use of CES1(as an intrahepatic marker of liver damage)and DPP-IV(as an extrahepatic marker of inflammation)for the accurate evaluation and tracking of liver-specific injury—an application that allows for the differentiation of liver damage and inflammatory liver injury.

Neonatal Exposure to the Dipeptidyl Peptidase-IV Inhibitors Diprotin A and Sitagliptin Induces Depression-Like Behavior, Anxiety, and Latent Aggression in Adolescent and Adult Rats

Emotional and motivational disorders in adults are often considered to be the result of altered neurodevelopment. Clinical and experimental data provide evidence that serine protease dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) is involved in the pathophysiology of psycho-emotional disorders. Recently, we have shown that adolescent and adult rats exhibit an increase in anxiety and depression-related behaviors after neonatal administration of a synthetic non-competitive inhibitor of DPP-IV, methionyl-2(S)-cyano-pyrrolidine. In the present study, we tested the effects of two competitive, selective DPP-IV inhibitors, sitagliptin (4 mg/kg) and diprotin A (2 mg/kg), administered at postnatal days 5 - 18 on the emotional and motivational behavior of adolescent and adult rats. We observed increased anxiety in one-month-old diprotin A- or sitagliptin-treated rats in the elevated plus maze;diprotin A also enhanced the animals’ anxiety score using a ranked scale for evaluating anxiety and phobias. In the sucrose consumption and preference test, depressive-like behavior was pronounced in both the diprotin A- and sitagliptin-treated one-month-old animals, while only the diprotin A-treated rats exhibited a decrease in sucrose consumption at the age of 2 months. The diprotin A-treated rats also demonstrated behavioral despair and decreased activity in the forced swimming test within 1 - 3 months of age. Increased aggression was observed in 1 - 3-month-old diprotin A-treated rats and in two-month-old sitagliptin-treated rats. These findings support the hypothesis that DPP-IV is involved in the genesis of emotional and motivational disorders. Additionally, the results show that diprotin А impairs the adolescent and adult rats’ behavior more significantly than sitagliptin when the animals were treated with the DPP-IV inhibitors in the early postnatal period.

Review on the Effect of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

Risk of pancreatic adverse events associated with the use of glucagon-like peptide-1 receptor agonist and dipeptidyl peptidase-4 inhibitor drugs: A systematic review and metaanalysis of randomized trials

AIM: To systematically assess risk of pancreatic adverse events with glucagon-like peptide-1(GLP-1) receptor agonist and dipeptidyl peptidase-4(DPP-4) inhibitor drugs.METHODS: We searched Pub Med, Embase, CINAHL, Cochrane review of clinical trials, pharmaceutical company clinical trials register, United States Food and Drug Administration website, European Medicines Agency website and Clinical Trials.gov for randomized controlled trials from inception to October 2013. Randomized control trial studies were selected for inclusion if they reported on pancreatic complication events and/or changes in pancreatic enzyme levels(serum amylase and serum lipase) as adverse events or as serious adverse events for patients who were on GLP-1 receptor agonist and DPP-4 inhibitor drugs. Two independent reviewers extracted data directly. We performed Peto odds ratio(OR) fixed effect meta-analysis of pancreatic adverse events a, and assessed heterogeneity with the I^2 statistic.RESULTS: Sixty-eight randomized controlled trials were eligible. A total of 60720 patients were included in our analysis of the association of risk of pancreatic complication events with GLP-1 agents. A total of 89 pancreatic related adverse events occurred among the GLP-1 agents compared to 74 events among the controls. There was a statistically significant increased risk of elevation of pancreatic enzymes associated with GLP-1 agents compared with control(Peto OR = 3.15, 95%CI: 1.56-6.39, P = 0.001, I2 = 0%). There was no statistically significant difference in the risk of pancreatic adverse event associated with GLP-1 agent compared with controls(Peto OR = 1.00, 95%CI: 0.73-1.37, P = 1.00, I2 = 0%). There were a total of 71 pancreatitis events in patients on GLP-1 agents and 56 pancreatitis events occurred in the control patients. There were 36 reports of pancreatic cancer in these studies. Of these cases, 2 used linagliptin, 2 used alogliptin, 1 used vildagliptin, 7 used saxagliptin while 6 used sitagliptin. The remaining 18 cases occurred among controls.CONCLUSION: Although GLP-1 based agents are associated with pancreatic enzyme elevation, we were unable to confirm a significant risk of pancreatitis or pancreatic cancer.

Expression of a novel dipeptidyl peptidase 8(DPP8)transcript variant,DPP8-v3,in human testis

Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction （RT-PCR） and Southern-blot analysis. Results： A new transcript variant of the human dipeptidyl peptidase （DPP8）, exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 （DPP8-v3）. The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. Conclusion： DPPS-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility. （Asian J Androl 2005 Sep; 7： 245-255）

二肽基肽酶3(DPP3)通过下调主要组织相容性复合体Ⅰ类链相关基因B(MICB)的表达抑制胃癌细胞的免疫逃逸

目的探究二肽基肽酶3(DPP3)通过调控主要组织相容性复合体Ⅰ类链相关基因B(MICB)的表达对胃癌细胞免疫逃逸的影响。方法敲低MKN-45人胃癌细胞DPP3、过表达MGC-803人胃癌细胞DPP3,观察细胞增殖、迁移能力变化及对自然杀伤(NK)细胞杀伤的反应性;采用全转录组测序筛得MICB基因,在过表达DPP3细胞中敲低MICB验证细胞行为变化。在C57小鼠验证敲除DPP3细胞的体内成瘤能力及组织中CD56+细胞浸润情况。结果敲除DPP3促进胃癌细胞增殖、迁移,降低MICB表达,对NK细胞杀伤效应不敏感;小鼠成瘤能力升高且组织中CD56^(+)细胞浸润降低。过表达DPP3的胃癌细胞则呈现相反结果。敲减MICB后能逆转DPP3高表达引起的细胞表型变化。结论DPP3通过下调MICB表达抑制胃癌细胞的免疫逃逸功能。

Effect of Urena lobataleaves extract on glucagon like peptide-1 serum level by inhibition of dipeptidyl peptidase-Ⅳ on diabetic rats

OBJECTIVE To investigate effect of Urenalobataleaves extract on glucagon like peptide-1(GLP-1)serum level by inhibition of dipeptidyl peptidase-Ⅳ(DPP-Ⅳ)on diabetic rat. METHODS This study uses control group post test only with male spraque dawley rats.Diabetic rats was induced by High Fructose Diet(HFD)and single dose streptozotocin 25mg·kg-1 bw intra peritoneal.The rat was administrated orally with ethanolic extract of U.lobataleaves in dose of 250,500 and 1000mg·kg-1 for 4weeks.Blood sample were collected from the tail vein at 15 min after oral glucose administration and then DPP-Ⅳserum level and GLP-1were examined using a rat elisa kits of DPP-Ⅳ and GLP-1.The data was analyzed using ANOVA test continued with LSD test(P<0.05).RESULTS The oral administration of U.lobataleaves extract at dose of 250,500 and 1000mg·kg-1 bw were able to prolong GLP-1 bioavaibility approximately 5,2and 2.5-fold respectively compared to diabetic group(P<0.05),while the DPP-Ⅳ serum level was decreased by 60%,50% and 40%(P<0.05),respectively.In diabetic groups,DPP-Ⅳ serum level was increased more and less 4-fold compared to normal group(P<0.05)while the GLP level were decreased by 8-fold(P<0.05).CONCLUSION U.lobataleaves extract could prolong GLP-1 bioavaibility by reducing of DPP-Ⅳserum level.This effect may be related to active compounds that act as an DPP-Ⅳinhibitor in U.lobata extract.

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of E3024, a Novel and Selective Dipeptidyl Peptidase-IV Inhibitor, in Healthy Japanese Male Subjects: Rash Development in Men and Its Possible Mechanism

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that was expected to be an antidiabetic agent. Its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) were investigated in a randomized, double-blind, placebo-controlled, ascending single-dose study in 48 healthy Japanese male subjects. Fasted subjects were orally administered E3024 (5, 10, 20, 40, or 80 mg) or placebo. E3024 was rapidly absorbed, with tmax values ranging between 0.33 and 3 h after dosing. The mean t1/2 ranged from 5.34 to 11.68 h. AUC0-inf and Cmax increased dose-proportionately. PK-PD relationship of E3024 was evaluated by using an Imax model, indicating that plasma E3024 concentrations and inhibitory effects of plasma DPP-IV activity were well correlated. The IC50 value was calculated as 33.7 ng/mL, which was consistent with in vitro data. Thus, E3024 showed a good PK profile and inhibited DPP-IV dose-dependently. Of 30 subjects administered E3024, 12 (40%) experienced adverse events (AEs). Dose escalation to 160 mg was abandoned owing to undesired subjective/objective findings in 4 of 6 subjects receiving 40 mg and 5 of 6 subjects receiving 80 mg. The most prominent AE was rash, but there were no serious AEs or deaths. The maximum tolerated dose was considered to be 20 mg. We hypothesized that histamine was a cause of the rash induction, and examined blood histamine levels of normal Fischer rats treated with E3024. Blood histamine levels were increased significantly by E3024 at 500 mg/kg (p < 0.001), but not by vildagliptin or valine-pyrrolidide (DPP-IV inhibitors) at the same dose. No blood histamine increases were observed in genetically mast cell-deficient Ws/Ws rats treated with E3024 at 500 mg/kg. In in vitro assays, E3024 induced histamine release from normal rat peritoneal mast cells in a concentration-dependent manner, but not from basophils. The structure-activity relationship study suggested that a piperazine group N-linked to the 2-position of the 5,6-membered fused heterocyclic rings was a key structural element for triggering histamine release.

5个原研二肽基肽酶4抑制剂的综合评价

目的:对5个原研二肽基肽酶4(DPP-4)抑制剂进行可量化的客观评价,为医疗机构遴选药品提供量化参考,为临床药品选择提供依据。方法:应用《中国医疗机构药品评价与遴选快速指南(第二版)》(以下简称“指南”)的评价体系,对5个原研DPP-4抑制剂的药学特性、有效性、安全性、经济性和其他属性等5个维度进行量化打分。结果:所有纳入评价的DPP-4抑制剂的评分均>70分,依次为西格列汀79.0分、维格列汀72.8分、沙格列汀76.1分、利格列汀78.7分、阿格列汀76.9分。结论:基于指南的标准,本次评价涉及的5个原研DPP-4抑制剂的评价结论均为“保留”,强推荐。但是,本次药品评价维度较多,涉及药品在各维度均有不同的优势,各医疗机构可根据评价细则及权重,按照医疗机构特点和实际需求对评价结果进行采用。

基于医院卫生技术评估的5种二肽基肽酶4抑制剂的临床应用情况

目的通过医院卫生技术评估(HB-HTA)对5种二肽基肽酶4抑制剂(DPP-4i)(西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀)进行评估,为医疗机构药品的遴选、临床的合理安全使用提供依据。方法通过HB-HTA,依照百分制评分体系,参考药品说明书、临床指南和文献,从安全性、有效性、经济型、创新性、适宜性和可及性等方面分别对5种DPP-4i进行评估。结果西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀得分分别为85.0、75.0、77.0、80.0、78.5分。评分差异主要在安全性、经济性、适宜性和可及性方面。西格列汀综合得分最高。结论HB-HTA评估DPP-4i结果比较合理,为医院药品遴选、安全合理使用提供依据。

利用受体配体亲和技术筛选黄芩中血管紧张素转换酶2和二肽基肽酶4抑制剂

目的筛选中药黄芩中血管紧张素转换酶2(ACE2)和二肽基肽酶4(DPP-4)抑制剂。方法以ACE2和DPP-4作为靶蛋白,利用受体配体亲和超滤和液质联用技术,对黄芩中与ACE2和DPP-4亲和的化合物进行筛选和分析,以筛选具有同时抑制ACE2和DPP-4的化合物。结果从黄芩中筛选出了5,7,2′,6′-4羟基黄酮、5,7,2′,5′-4羟基-8,6′-二甲氧基黄酮、白杨素-7-O-葡萄糖醛酸苷、黄芩素-6-O-葡萄糖醛酸苷、千层纸素A-7-O-葡萄糖醛酸苷、汉黄芩苷、白杨素、千层纸素A,可以同时亲和抑制ACE2和DPP-4,具有潜在的抗新型冠状病毒的作用。结论从黄芩中筛选出与新型冠状病毒肺炎有关的靶蛋白抑制剂,具备潜在开发价值。

二肽基肽酶-Ⅳ有机小分子荧光探针的研究进展

二肽基肽酶-IV(DPP-IV)是一种重要的跨膜糖蛋白水解酶,与各种生理过程和疾病密切相关,检测DPP-IV的有机小分子荧光探针被相继报道,是当前研究生物酶检测的热点。首次综述了用于DPP-IV体外和体内检测及成像的3类有机小分子荧光探针,分别是非近红外荧光探针(λ_(em)<650nm)、近红外荧光探针(λ_(em)>650nm)和双光子荧光探针,对比并总结了三种探针的设计原理、结构特点、生物应用情况及其在DPP-IV相关疾病诊断中的应用,并探讨了DPP-IV活性检测在未来发展方向上所面临的挑战。