Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging

The use of radiolabelled antibodies and antibody‐derived recombinant constructs has shown promise for both imaging and therapeutic use. In this context, the biotin–avidin/streptavidin pairing, along with the inverse‐electron‐demand Diels–Alder (iEDDA) reaction, have found application in pretargeting approaches for positron emission tomography (PET). This study reports the fluorinase‐mediated transhalogenation [5′‐chloro‐5′‐deoxyadenosine (ClDA) substrates to 5′‐fluoro‐5′‐deoxyadenosine (FDA) products] of two antibody pretargeting tools, a FDA‐PEG‐tetrazine and a [¹⁸F]FDA‐PEG‐biotin, and each is assessed either for its compatibility towards iEDDA ligation to trans‐cyclooctene or for its affinity to avidin. A protocol to avoid radiolytically promoted oxidation of biotin during the synthesis of [¹⁸F]FDA‐PEG‐biotin was developed. The study adds to the repertoire of conjugates for use in fluorinase‐catalysed radiosynthesis for PET and shows that the fluorinase will accept a wide range of ClDA substrates tethered at C‐2 of the adenine ring with a PEGylated cargo. The method is exceptional because the nucleophilic reaction with [¹⁸F]fluoride takes place in water at neutral pH and at ambient temperature.     

微生物法测定特殊医学用途配方食品中生物素含量的不确定度评定

特殊医学用途配方食品是部分人群摄取营养的唯一来源,其中生物素的准确定量具有重要的意义。采用GB 5009.259-2016中规定的微生物法进行生物素含量测定,并评定了标准不确定度和扩展不确定度,测定结果生物素含量为(27.16±1.15)μg/100g, p=95%, k=2。分析了各个分量对不确定度的贡献,结果表明:实验重复性为主要影响因素,为微生物法测定生物素的关键控制点。     

设计与制备基于链霉亲和素-生物素接合的铁蛋白-金纳米粒子二聚体

金纳米粒子二聚体在纳米科学技术的诸多领域中展示出引人注目的成就,但金纳米粒子二聚体的制备仍然是一项具有挑战性的工作。文章对基于链霉亲和素-生物素接合的铁蛋白-金纳米粒子二聚体的设计与制备进行了研究,通过混合生物素标记的突变型铁蛋白亚基和野生型铁蛋白亚基包覆金纳米粒子,用链霉亲和素将两个装载了金纳米粒子的铁蛋白连接,透射电子显微镜测试结果证实了上述设计方案的有效性。该方案可广泛应用于制备含有其他金属核的纳米粒子二聚体体系。     

Lactation performance by dairy cows fed supplemental biotin and a B-vitamin blend

The objective of Trial 1 was to evaluate in dairy cows the effects of dietary supplementation with biotin and a B-vitamin blend on dry matter intake (DMI), milk yield, composition and component yields, total tract nutrient digestion, and plasma metabolites. Twenty-four multiparous Holstein cows averaging 46 +/- 8 d in milk at trial initiation were randomly assigned to treatments in a replicated 4 x 4 Latin square design with 28 d periods. The four treatments were: 1) a control diet (C) with no supplemental B-vitamins; 2) C plus supplemental biotin at 20 mg/d (B); 3) C plus supplemental thiamin (150 mg/d), riboflavin (150 mg/d), pyridoxine (120 mg/d), B12 (0.5 mg/d), niacin (3000 mg/d), pantothenic acid (475 mg/d), folic acid (100 mg/d), and biotin (20 mg/d) (BBVIT1X); 4) C plus supplemental thiamin (300 mg/d), riboflavin (300 mg/d), pyridoxine (240 mg/d), B12 (1.0 mg/d), niacin (6000 mg/d), pantothenic acid (950 mg/d), folic acid (200 mg/d), and biotin (40 mg/d) (BBVIT2X). Intake of DM was increased 0.7 kg/d for B vs. C and BBVIT1X and 1.3 kg/d for B vs. BBVIT2X. Milk yield was increased 1.7 kg/d for B vs. C. For BBVIT1X, milk yield was similar to B and BBVIT2X and tended to be higher than C. Yields of milk protein and lactose but not fat were higher for B than C. For BBVIT1X, milk component yields were similar to B and tended to be higher than C, with the exception of lactose yield where BBVIT1X was higher than C. The objective of Trial 2 was to evaluate DMI and milk yield, composition and component yields by dairy cows fed diets supplemented with either 40 mg/d biotin or the B-vitamin blend (BBVIT1X) compared to cows supplemented with 20 mg/d dietary biotin. Neither the 40 mg/d biotin treatment nor the B-vitamin blend enhanced lactation performance over the 20 mg/d biotin treatment. Biotin efficacy in short-term trials suggests that biotin may improve milk yield directly via effects on intake and (or) nutrient metabolism rather than indirectly via improved hoof health. More research is needed to determine the mode of action for supplemental dietary biotin.     

生物主动靶向型高分子药物载体的研究现状

许多经普通途径给药的药物由于未修饰,不能够以有效的浓度作用于目的器官,或者由于易被代谢而不能维持有效的给药时间。人们已经尝试许多靶向药物载体与系统来解决这些问题。总结了近几年来生物主动靶向型高分子药物载体的研究进展。针对叶酸介导,生物素介导,以及其他常见官能团介导的药物载体,从载体的合成,细胞检测以及动物实验等进行概述。生物主动靶向型高分子药物载体可以有效提高药物的生物利用度,减少药物的毒副作用。     

Impedimetric Measurements for Monitoring Avidin-Biotin Interaction on Self-Assembled Monolayer

Avidin-biotin has been controllable immobilized on the surface of gold electrodes using mercaptopropionic acid as self-assembled monolayer. Electrochemical impedance spectroscopy (EIS) was employed to investigate the changes that appear at the electrode surface in the presence of a redox mediator, K₃[Fe(CN)₆]. An electrical model more complex than that in other studies was used to interpret the EIS measurements (Randles circuit). This model is very useful because it takes into consideration both the transfer of electrons at the electrode/electrolyte interface and the diffusion of redox species through the double layer. The model allowed us to determine some important parameters like solution resistance R_sol, charge-transfer resistance R_ct, double-layer capacitance C_dl, Warburg resistance R_W, and the diffusion time constant τ. The EIS results proved that immobilization of avidin-biotin increased the charge-transfer resistance R_ct, due to the insulating character of these molecules.     

一种生物素改性聚乳酸生物材料的制备与性能研究

研究试图通过本体改性,将生物素接枝到聚乙二醇接枝聚乳酸(PPLA)上,以改善聚乳酸微球在药物缓释应用中血液循环时间短和无主动靶向性的缺点.在本实验室制备的聚乙二醇接枝改性聚乳酸的基础之上,采用N-羟基琥珀酰亚胺活化酯法,将生物素接枝到PPLA上,制备生物素改性聚乳酸(BPLA),通过茚三酮显色、核磁共振(1H-NMR)...     

Synthesis and characterization of novel poly(γ‐benzyl‐L‐glutamate) derivatives tailored for the preparation of nanoparticles of pharmaceutical interest

Four poly(γ‐benzyl‐L ‐glutamate) (PBLG) derivatives bearing at one end specific groups were synthesized by ring‐opening polymerization of the corresponding γ‐benzyl‐L ‐glutamate N‐carboxyanhydride using different amine‐terminated initiators. These moieties were chosen to introduce, on demand, specific functionalities in nanoparticles of pharmaceutical interest. The PBLG and PBLG derivatives were characterized by ¹H NMR, viscosimetry, Fourier transform infrared spectroscopy and differential scanning calorimetry. Nanoparticles smaller than 100 nm in diameter could be easily prepared from these PBLG derivatives by slight modification of a known nanoprecipitation technique. Copyright © 2006 Society of Chemical Industry     

生物素化普鲁兰多糖纳米颗粒制备与表征

合成生物素化普鲁兰多糖衍生物(BP),采用纳米沉淀法制备纳米颗粒(BPNs),考察制备条件对纳米颗粒性质影响,为进一步将其作为药物载体的研究提供基础.通过酯化反应将生物素羧基与普鲁兰多糖连接,生成的衍生物BP通过FI-IR和1H-NMR表征,取代度采用电感耦合等离子体光谱仪(ICP)确定;BPNs进行透射电镜、动态光散射仪和ζ电位仪表征与检测,颗粒表面生物素采用Quant*TagTM Biotin Kit生物素测定试剂盒测定.获得取代度21(BP1),46(BP2),81(BP3)3种衍生物,其中BP2和BP3能够制备纳米颗粒(LBPNs,HBPNs).纳米颗粒呈球形,表面光滑规整,平均粒径100～300nm,水中ζ电位在一17mV左右.制备过程中,粒径随BP浓度(10～50mg/ml)增加而增加((136.2±46.8)nm,(190.8±89.6)nm和(254.5±140.0)nm).调整水相组成为水:元水乙醇(v/v)1:1和1:2时粒径分别为(170.7±30.4)nm和(158.8±21.0)nm.HBPNs和LBPNs表面的生物素量为衍生物的(1.9±0.03)%和(2.0±0.04)%.生物素化普鲁兰多糖衍生物通过纳米沉淀法能制备出纳米颗粒,颗粒表面存在有生物素,颗粒性质受制备条件影响.