人源化甲状腺素脱碘酶单链抗体的结构模拟

以四碘甲状腺素原氨酸为半抗原,从人噬菌体展示半合成单链抗体库中筛选与半抗原有特异结合性的单链抗体E3,并测定了E3的一级结构,同时用计算机模拟了其空间结构.     

Solid phase extraction for the speciation and preconcentration of inorganic selenium in water samples: A review

Selenium is an essential element for the normal cellular function of living organisms. However, selenium is toxic at concentrations of only three to five times higher than the essential concentration. The inorganic forms (mainly selenite and selenate) present in environmental water generally exhibit higher toxicity (up to 40 times) than organic forms. Therefore, the determination of low levels of different inorganic selenium species in water is an analytical challenge. Solid-phase extraction has been used as a separation and/or preconcentration technique prior to the determination of selenium species due to the need for accurate measurements for Se species in water at extremely low levels. The present paper provides a critical review of the published methods for inorganic selenium speciation in water samples using solid phase extraction as a preconcentration procedure. On the basis of more than 75 references, the different speciation strategies used for this task have been highlighted and classified. The solid-phase extraction sorbents and the performance and analytical characteristics of the developed methods for Se speciation are also discussed.     

内质网硒蛋白的研究进展

硒是哺乳动物必需的一种微量营养元素,主要以硒代半胱氨酸的形式存在于各种硒蛋白中,硒的主要生物功能通过硒蛋白实现.在25种哺乳动物硒蛋白中,有7种硒蛋白位于内质网,分别为2型脱碘酶、15-kDa硒蛋白、硒蛋白M、硒蛋白T、硒蛋白K、硒蛋白S和硒蛋白N.除了2型脱碘酶外,对其余内质网硒蛋白知之甚少.最近一些研究显示,一些内质网硒蛋白在氧化还原平衡调节、蛋白质折叠质量控制、错误折叠蛋白从内质网逆向转运至胞质、Ca2+稳态调节、内质网应激调节及炎症调节等过程中发挥作用.本文介绍了每种内质网硒蛋白的结构、功能及其生理和病理作用的一些最新研究进展,并对未来需要研究的内容进行了展望.     

Halogen Bonding Controls the Regioselectivity of the Deiodination of Thyroid Hormones and their Sulfate Analogues

The type 1 iodothyronine deiodinase (1D‐1) in liver and kidney converts the L ‐thyroxine ( T4 ), a prohormone, by outer‐ring (5′) deiodination to biologically active 3,3′,5‐triiodothyronine ( T3 ) or by inner‐ring (5) deiodination to inactive 3,3′,5′‐triiodothronine ( rT3 ). Sulfate conjugation is an important step in the irreversible inactivation of thyroid hormones. While sulfate conjugation of the phenolic hydroxyl group stimulates the 5‐deiodination of T4 and T3 , it blocks the 5′‐deiodination of T4 . We show that thyroxine sulfate ( T4S ) undergoes faster deiodination as compared to the parent thyroid hormone T4 by synthetic selenium compounds. It is also shown that ID‐3 mimics, which are remarkably selective to the inner‐ring deiodination of T4 and T3 , changes the selectivity completely when T4S is used as a substrate. From the theoretical investigations, it is observed that the strength of halogen bonding increases upon sulfate conjugation, which leads to a change in the regioselectivity of ID‐3 mimics towards the deiodination of T4S . It has been shown that these mimics perform both the 5′‐ and 5‐ring deiodinations by an identical mechanism.     

The role of the halogen bond in iodothyronine deiodinase: Dependence on chalcogen substitution in naphthyl-based mimetics

The effects on the activity of thyroxine (T4) due to the chalcogen replacement in a series of peri-substituted naphthalenes mimicking the catalytic function of deiodinase enzymes are computationally examined using density functional theory. In particular, T4 inner-ring deiodination pathways assisted by naphthyl-based models bearing two tellurols and a tellurol-thiol pair in peri-position are explored and compared with the analogous energy profiles for the naphthalene mimic having two selenols. The presence of a halogen bond (XB) in the intermediate formed in the first step and involved in the rate-determining step of the reaction is assumed to facilitate the process increasing the rate of the reaction. The rate-determining step calculated energy barrier heights allow rationalizing the experimentally observed superior catalytic activity of tellurium containing mimics. Charge displacement analysis is used to ascertain the presence and the role of the electron density charge transfer occurring in the rate-determining step of the reaction, suggesting the incipient formation or presence of a XB interaction. © 2019 Wiley Periodicals, Inc.     

Halogen Bonding Interactions of Polychlorinated Biphenyls and the Potential for Thyroid Disruption

Polychlorinated biphenyl (PCB) flame retardants are persistent pollutants and inhibit neurodevelopment, particularly in the early stages of life. Halogen bonding (XB) to the iodothyronine deiodinases (Dio) that modulate thyroid hormones (THs) is a potential mechanism for endocrine disruption. Cl⋅⋅⋅Se XB interactions of PCBs with SeMe⁻, a small model of the Dio active site selenocysteine, are compared with previous results on polybrominated diphenylethers (PBDEs) and THs using density functional theory. PCBs generally display weaker XB interactions compared to PBDEs and THs, consistent with the dependence of XB strength on the size of the halogen (I>Br>Cl). PCBs also do not meet a proposed energy threshold for substrates to undergo dehalogenation, suggesting they may behave as competitive inhibitors of Dio in addition to other mechanisms of endocrine disruption. XB interactions in PCBs are position-dependent, with ortho interactions slightly more favorable than meta and para interactions, suggesting that PCBs may have a greater effect on certain classes of Dio. Flexibility of PCBs around the biphenyl C−C bond is limited by ortho substitutions relative to the biphenyl linkage, which may contribute to the ability to inhibit Dio and other TH-related proteins.