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61.
62.
Bo Zhang Giancarlo Pascali Naomi Wyatt Lidia Matesic Mitchell A. Klenner Tiffany R. Sia Adam J. Guastella Massimiliano Massi Andrea J. Robinson Benjamin H. Fraser 《Journal of labelled compounds & radiopharmaceuticals》2018,61(11):847-856
Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [18F]ethenesulfonyl fluoride ([18F]ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [18F]ESF was optimised using a microfluidic reactor under both carrier‐added (c.a.) and no‐carrier‐added (n.c.a.) conditions, affording, in a straightforward procedure, 30‐50% radiochemical yield (RCY) for c.a. [18F]ESF and 60‐70% RCY for n.c.a. [18F]ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [18F]ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging. 相似文献
63.
Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes 下载免费PDF全文
Kusum Vats Drishty Satpati Rohit Sharma Chandan Kumar Haladhar Dev Sarma Sharmila Banerjee 《Journal of labelled compounds & radiopharmaceuticals》2018,61(2):68-76
The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG2‐c(NGR), were synthesized, radiolabeled with 99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. 相似文献
64.
Ajay Ghosh Chalasani Utpal Roy Sushma Nema 《International journal of antimicrobial agents》2018,51(1):89-97
A strong antistaphylococcal peptide (ASP-1) from Bacillus subtilis URID 12.1 strain that is active against cefoxitin- and methicillin-resistant Staphylococcus aureus clinical isolates was purified to homogeneity by solvent extraction, silica gel-based adsorption chromatography and reversed-phase high-performance liquid chromatography. The peptide sequence of ASP-1 as determined by MALDI-TOF/MS and ESI-FTICR-MS was acetylated Phe-Thr-Ala-Val-Dhb-Phe-Ile/Leu. The peptide was further analysed by alkaline hydrolysis, ESI-Q-TOF-MS and an ion mobility assay, which detected the presence of a lactone ring in the intact peptide and a cyclic nature, subsequently revealing the linearised peptide sequence as acPhe-Leu-Phe-Thr-Val-Ala-Dhb. Based on the molecular mass (804.5 Da), peptide sequence and amino acid composition, ASP-1 was identified as a lactone ring-containing peptide similar to TL-119, a poorly studied cyclic depsipeptide. Circular dichroism spectroscopy revealed its predominantly random structure in aqueous solution and its β-sheet conformation in methanol. Minimum inhibitory concentrations (MICs) of the purified peptide against S. aureus and methicillin-resistant S. aureus (MRSA) ranged from 2?µg/mL to 64?µg/mL. At sub-MICs and 1× MIC, ASP-1 showed a strong antibiofilm characteristic. ASP-1 at a concentration of 128?µg/mL did not show haemolytic activity, and no cytotoxicity was observed against hepatic carcinoma and breast carcinoma cell lines at the same concentration. Peptide ASP-1 with anti-MRSA and antibiofilm abilities and non-haemolytic and non-cytotoxic properties has not been reported previously. These findings suggest that it may serve as a lead molecule for developing alternative topical antibacterial agents. 相似文献
65.
目的探究抗氧化肽AOP_1促进小鼠皮肤烫伤创面愈合修复的作用及机制。方法选用DCFH-DA检测细胞内活性氧(ROS)的变化;通过细胞增殖与迁移实验检测药物毒性及对创面愈合的影响。采用直径1 cm铜柱80℃水浴2min、紧贴小鼠皮肤10 s的方法制备烫伤模型,观察烫伤创面愈合情况;并用HE和Masson三色染色观察AOP_1对皮肤烫伤创面愈合修复的作用;检测小鼠全皮组织中MDA含量和SOD活性。结果在细胞水平上,抗氧化肽AOP_1能够明显降低HaCaT和L929细胞内ROS的含量,促进细胞迁移和增殖。与对照组相比,AOP_1组小鼠皮肤创面愈合时间短、愈合率高,结痂面积小,可明显降低烫伤创伤组织中炎症反应及MDA的含量;HE和Masson染色也证实了AOP_1对烫伤创面愈合修复的促进作用。结论具有天然活性的抗氧化肽AOP_1可能通过减轻烫伤引起的氧化应激,促进小鼠皮肤烫伤创面的愈合修复。 相似文献
66.
摘 要 目的:使用网状Meta分析系统评价胰高血糖素样肽1受体激动剂(GLP-1 RAs)类降糖药对2型糖尿病(T2DM)患者头疼和眩晕的影响。方法:系统检索Medline、Embase、Clinical trials和Cochrane数据库中(截止2017年6月23日)比较GLP-1 RAs与传统降糖药或安慰剂对头疼和眩晕发生风险影响的随机对照试验(RCT),采用贝叶斯网状Meta分析对纳入的研究进行分析。结果:共纳入100项RCTs,包括15种干预措施:8种GLP-1 RAs类降糖药(艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽、阿必鲁肽、杜拉鲁肽、索玛鲁肽)、安慰剂、2种二肽基肽酶-4(DPP-4)抑制剂(西格列汀和维格列汀)和4种传统降糖药(胰岛素、二甲双胍、磺脲类、噻唑烷二酮类)。网状Meta分析结果显示:与胰岛素相比,艾塞那肽(OR=1.35,95%CI:1.13~1.60)、利拉鲁肽(OR=1.35,95%CI:1.12~1.62)、利西拉来(OR=1.59,95%CI:1.22~2.06)和他司鲁肽(OR=1.78,95%CI:1.33~2.37)致T2DM患者发生头疼的风险增加;与安慰剂、胰岛素及噻唑烷二酮相比,艾塞那肽和利拉鲁肽显著增加了眩晕发生的风险(OR的取值范围为1.56~2.56)。此外,后验概率显示,致T2DM患者发生头疼风险最高的前三位为艾塞那肽缓释剂、二甲双胍、他司鲁肽;致T2DM患者发生眩晕风险最高的前三位为利拉鲁肽、利西拉来和艾塞那肽。结论:艾塞那肽缓释剂和他司鲁肽显著增加了头疼的发生风险,利拉鲁肽显著增加了眩晕的发生风险,但仍建议开展相应的大型前瞻性研究加以验证。 相似文献
67.
目的 探讨血清胃泌素释放肽前体(ProGRP)在小细胞肺癌(SCLC)鉴别诊断、疗效监测中的临床意义。 方法 收集2015年12月至2017年7月在安徽省立医院西区诊治的334例患者资料,其中SCLC134例,NSCLC和肺良性疾病(BLD)患者各100例。回顾性分析其化疗前血清ProGRP、神经烯醇化酶(NSE)和癌胚抗原(CEA)的水平及治疗过程中血清ProGRP水平变化,评估血清ProGRP在SCLC诊治中临床意义。 结果 (1)血清ProGRP和NSE在SCLC患者组均显著高于NSCLC组和肺良性疾病(BLD)组,P<0.05。(2)受试者工作特征曲线(ROC)曲线分析cut-off值取185.25时,血清ProGRP对SCLC诊断敏感性74.6%,特异性100%。(3)血清ProGRP水平与SCLC患者临床特征无相关性。(4)化疗前SCLC治疗有效组和无效组血清ProGRP水平差异无统计学意义(1 556 比 1 025 ng·L-1,P>0.05),治疗有效组血清ProGRP进行性下降,末次化疗后血清ProGRP与治疗前差异有统计学意义 (121.8 ng·L-1,P<0.05)。治疗无效组血清ProGRP水平在化疗2周期后下降,随后上升。末次化疗后血清ProGRP水平与化疗前差异无统计学意义(989.7 ng·L-1,P>0.05)。 结论 血清ProGRP水平对SCLC鉴别诊断具有高度特异性,SCLC患者治疗过程中ProGRP水平与治疗疗效呈负相关,对SCLC鉴别诊断和疗效预测的具有一定临床意义。 相似文献
68.
Baozhen Zhang Guogang Cheng Mingbin Zheng Jinyu Han Baobei Wang Mengxia Li 《Drug delivery》2018,25(1):461-471
Gestational trophoblastic neoplasia (GTN) can result from the over-proliferation of trophoblasts. Treatment of choriocarcinoma, the most aggressive GTN, currently requires high doses of systemic chemotherapeutic agents, which result in indiscriminate drug distribution and severe toxicity. To overcome these disadvantages and enhance the chemotherapeutic efficacy, chondroitin sulfate A (CSA)-binding nanoparticles were developed for the targeted delivery of doxorubicin (DOX) to choriocarcinoma cells using a synthetic CSA-binding peptide (CSA-BP), derived from malarial protein, which specifically binds to the CSA exclusively expressed in the placental trophoblast. CSA-BP-conjugated nanoparticles rapidly bonded to choriocarcinoma (JEG3) cells and were efficiently internalized into the lysosomes. Moreover, CSA-BP modification significantly increased the anti-cancer activity of the DOX-loaded nanoparticles in vitro. Intravenous injections of CSA-BP-conjugated nanoparticles loaded with indocyanine green (CSA-INPs) were rapidly localized to the tumor. The CSA-targeted nanoparticles loaded with DOX (CSA-DNPs) strongly inhibited primary tumor growth and, more importantly, significantly suppressed metastasis in vivo. Collectively, our results highlight the potential of the CSA-BP-decorated nanoparticles as an alternative targeted delivery system of chemotherapeutic agents for treating choriocarcinoma and for developing new GTN therapies based on drug targeting. 相似文献
69.
Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed. The microstructure and in vitro release of MT was assayed. The protective role of MT-loaded SAP (SAP-MT) hydrogel on renal mitochondrial injury, tubular apoptosis, and inflammation was evaluated in mice at five days after ischemia-reperfusion injury (IRI). Our results showed that KLDD could self-assemble into cross-linked nanofiber hydrogel and it had lower release rate than free MT and KLD hydrogel. Compared to IRI and free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS) and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice showed less renal tubular cell apoptosis, kidney injury marker kidney injury molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors expression, and macrophages infiltration than those of IRI and free MT mice. This study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial protection role than free MT and thus improved the long-term outcomes of AKI. 相似文献
70.
Meifang Zhai Yuli Wang Ligang Zhang Meng Liang Shiyao Fu Lin Cui 《Drug delivery》2018,25(1):1013-1024
Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature of drugs and the physiological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). An ideal glioma-targeted delivery system must be sufficiently potent to cross the BBB and BBTB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available apoferritin nanocage-based drug delivery system with the modification of GKRK peptide ligand (GKRK-APO). Apoferritin (APO), an endogenous nanosize spherical protein, can specifically bind to brain endothelial cells and glioma cells via interacting with the transferrin receptor 1 (TfR1). GKRK is a peptide ligand of heparan sulfate proteoglycan (HSPG) over-expressed on angiogenesis and glioma, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect of GKRK peptide and parent APO, GKRK-APO displayed higher glioma localization than that of parent APO. After loading with VCR, GKRK-APO showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that GKRK-APO is an important potential drug delivery system for glioma-targeted therapy. 相似文献