Opioid receptor antagonist affinity ligands: 6β-bromoacetamido-6-desoxynaltrexone and 6β-thioglycolamido-6-desoxynaltrexone

The present study, utilizing thioglycolamido as the reactive group, describes the synthesis and pharmacology of a new opioid antagonist affinity ligand, 6-thioglycolamido-6-desoxynaltrexone (TAN) and compares TAN with a related known compound, 6-bromoacetamido-6-desoxynaltrexone (BAN). Both compounds were tested for their reversible and irreversible inhibition of [³H]naloxone binding to calf brain membranes. Reversible binding of BAN and TAN had K_i values of 1×10^–9 and 1×10^–10 M, respectively as determined by log probit plots. Irreversible binding was determined after extensive washing to remove all non-covalently bound ligand. At a concentration of 5×10^–8 and 1×10^–8 M for BAN and TAN irreversible binding was inhibited 50% of the maximum value. A study of the time course of irreversible inhibition of [³H]naloxone binding revealed that maximal inhibition occurred within 5 min with a concentration of 1×10^–7 M of either agent. TAN but not BAN when administered systematically to mice produced an antinociceptive effect as measured by the writhing test. When administered intracerebraventricularly BAN did not block morphine-induced analgesia for more than 2 hr; whereas, with a single ED₅₀ dose of 20 nmoles of TAN i.c.v. morphine-induced analgesia was almost completely blocked for a period of over 24 hr, as determined by the tail flick test. Although the SH group of TAN were required for the covalent interaction with opioid receptors, the site of TAN's interaction appears to involve other than protein SH groups.     

6′-substituted and 6′,6″-disubstituted derivatives of raffinose

The reaction of 6′-chloro-6′-deoxyraffinose deca-acetate with a variety of nucleophilic anions (Br^-,I^-,N^-₃) gave the corresponding 6′-substituted raffinoses. The 6′-azide was further converted into 6′-amino-6′-deoxyraffinose, isolated as its N-acetyl derivative, and silver fluoride-induced elimination of hydrogen iodide from the 6′-iodide gave the 6′-deoxy-5′-ene. Treatment of 6′-chloro-6′-deoxyraffinose and 6′,6″-dichloro-6′,6″-dideoxyraffinose with base afforded, respectively, 3′,6′-anhydro-and 3′,6′;3″,6″-dianhydro-raffinose in high yields. In addition, the dichloride was converted into 6′,6″-diazido-6′,6″-dideoxyraffinose.     

锌指蛋白6(ZBED6)研究进展

锌指蛋白6(ZBED6)基因是新发现的一个转录调控因子,与肌肉的生长发育密切相关,可调控胰岛素样生长因子2(Insulin-like growth factor 2,IGF2)在内的多种基因的表达,为哺乳动物特有,序列高度保守。IGF2作为重要的生长调节因子,内含子3区域可与ZBED6结合,ZBED6的结合可抑制IGF2表达,进而调控细胞的增殖分化和肌肉的生长发育。总结了目前对ZBED6基因的生理功能研究进展,已有研究表明ZBED6可抑制IGF2的表达,促进骨骼肌、心脏、肝脏、肾脏等器官的生长发育,降低脂肪沉积,体内蛋白质、脂质等生物大分子的代谢过程也随之发生变化,ZBED6在糖尿病、癌症的发展过程中均发挥着重要的调控作用。此外,还总结了影响ZBED6表达的多种因素,包括碱基突变、DNA甲基化、组蛋白修饰以及回文序列等。最后,展望了ZBED6的实际应用潜力,其作为一个与肌肉生长发育密切相关的转录因子,可通过敲除ZBED6促进肌肉生长,为瘦肉型动物的遗传育种提供了新的思路。     

怪兽猎人6

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成纤维细胞生长因子6(FGF6)的研究进展

成纤维细胞生长因子6(fibroblast growth factor 6,FGF6)是成纤维细胞生长因子家族(FGFs)的成员之一,主要通过与酪氨酸激酶受体(fibroblast growth factor receptor,FGFR)1和4结合发挥其生物学活性。研究发现,人FGF6几乎都积聚在肌源性细胞系中,参与肌源性细胞系的增殖及分化,在肌肉修复和再生过程中起重要作用,同时它还是一个重要的调节骨生成和骨重建的因子;FGF6在心脏中也有表达,进一步试验结果表明其具有促进心肌细胞增殖及保护心肌细胞凋亡的作用;在成体睾丸和乳腺癌中也检测到有FGF6的转录物,表明其在肿瘤发生发展中的作用。目前,FGF6在多种疾病中的功能和相关机制仍有待进一步研究和确认,但其所具备的生物学活性尤其是在肌肉再生方面具有重要的意义和巨大的应用潜力。     

医用胶合剂MK-6

胶合剂MK-6是一种用于肺外科、血管外科、泌尿外科、神经科等手术时供胶合软组织用的一种胶合剂。胶合剂MK-6是一种快速凝聚剂,在与人体器官软组织接触时,发生聚合作用,其结果能在需连合部位的表面形成一个很坚固并具有弹性的膜,整个胶合过程在2～3分     

溶血磷脂酸受体6

溶血磷脂酸受体6(lysophosphatidic acid receptor 6,LPA6)作为最晚确定的溶血磷脂酸(lysophosphatidic acid,LPA)受体,近年来多项研究发现LPA6参与毛囊发育过程,与人体毛发稀少症存在相关性;并可减弱细胞间的粘附作用。且最近相关研究报道指出,LPA6在肿瘤的发展过程中同样扮演重要角色。本文将汇集LPA6相关知识,对其研究现状进行综述。     

人类疱疹病毒6型

<正>人类疱疹病毒6型(HHV-6)最先是从淋巴细胞增生性疾病患者中分离出来的一种新的疱疹病毒。其抗原性和遗传学特性与疱疹病毒1型,疱疹病毒2型,巨细胞病毒(CMV),水痘一带状疱疹病毒(VZV)及EBV均不相同。后来发现HHV-6是幼儿急疹(ES)的病原体。本文就HHV-6的血清流行病学,从ES患儿中的分离检测,与HHV— 6感染有关的疾病及其病毒学特性等综述如下。     

6 or 9?

In this article the author offers an original interpretation of patterns found on the world's most ancient felts (Fifth Century BCE). These artifacts have been recovered from frozen burial mounds in the Altai Mountains. The interpretation presented here constitutes a new approach to the study of ornamentation as a system of symbols.     

6C6鼠-人嵌合抗体的纯化及鉴定

采用基因工程技术 ,将小鼠 6C6单克隆抗体可变区基因与人抗体恒定区基因连接 ,构建了鼠 人 6C6嵌合抗体基因 ,并在CHO细胞中高效表达 .利用ProteinA亲和层析柱从细胞培养上清中分离纯化 6C6嵌合抗体 ,得到电泳纯度大于 98%的 6C6嵌合抗体 ,其重链 (5 5kD)和轻链 (2 4kD)符合IgG相对分子质量的理论值 .Western印迹、细胞免疫荧光和免疫组织化学实验结果均呈阳性 .表明6C6嵌合抗体可识别人乳腺癌细胞表面上的肿瘤相关抗原 ,保持了 6C6单克隆抗体的特性 ,为后续的研究工作奠定了基础