A phosphotyrosine-imprinted polymer receptor for the recognition of tyrosine phosphorylated peptides

Hyperphosphorylation at tyrosine is commonly observed in tumor proteomes and, hence, specific phosphoproteins or phosphopeptides could serve as markers useful for cancer diagnostics and therapeutics. The analysis of such targets is, however, a challenging task, because of their commonly low abundance and the lack of robust and effective preconcentration techniques. As a robust alternative to the commonly used immunoaffinity techniques that rely on phosphotyrosine(pTyr)-specific antibodies, we have developed an epitope-imprinting strategy that leads to a synthetic pTyr-selective imprinted polymer receptor. The binding site incorporates two monourea ligands placed by preorganization around a pTyr dianion template. The tight binding site displayed good binding affinities for the pTyr template, in the range of that observed for corresponding antibodies, and a clear preference for pTyr over phosphoserine (pSer). In further analogy to the antibodies, the imprinted polymer was capable of capturing short tyrosine phosphorylated peptides in the presence of an excess of their non-phosphorylated counterparts or peptides phosphorylated at serine.     

Antioxidant activity of the anti-inflammatory compound ebselen: a reversible cyclization pathway via selenenic and seleninic acid intermediates

A revised mechanism that accounts for the glutathione peroxidase (GPx)-like catalytic activity of the organoselenium compound ebselen is described. It is shown that the reaction of ebselen with H(2)O(2) yields seleninic acid as the only oxidized product. The X-ray crystal structure of the seleninic acid shows that the selenium atom is involved in a noncovalent interaction with the carbonyl oxygen atom. In the presence of excess thiol, the Se--N bond in ebselen is readily cleaved by the thiol to produce the corresponding selenenyl sulfide. The selenenyl sulfide thus produced undergoes a disproportionation in the presence of H(2)O(2) to produce the diselenide, which upon reaction with H(2)O(2), produces a mixture of selenenic and seleninic acids. The addition of thiol to the mixture containing selenenic and seleninic acids leads to the formation of the selenenyl sulfide. When the concentration of the thiol is relatively low in the reaction mixture, the selenenic acid undergoes a rapid cyclization to produce ebselen. The seleninic acid, on the other hand, reacts with the diselenide to produce ebselen as the final product. DFT calculations show that the cyclization of selenenic acids to the corresponding selenenyl amides is more favored than that of sulfenic acids to the corresponding sulfenyl amides. This indicates that the regeneration of ebselen under a variety of conditions protects the selenium moiety from irreversible inactivation, which may be responsible for the biological activities of ebselen.     

Complex Cascade Reaction Networks via Cross β Amyloid Nanotubes

Biocatalytic reaction networks integrate complex cascade transformations via spatial localization of multiple enzymes confined within the cellular milieu. Inspired by nature's ingenuity, we demonstrate that short peptide‐based cross‐β amyloid nanotubular hybrids can promote different kinds of cascade reactions, from simple two‐step, to multistep, to complex convergent cascades. The compartmentalizing ability of paracrystalline cross‐β phases was utilized to colocalize sarcosine oxidase (SOX) and hemin as an artificial peroxidase. Further, the catalytic potential of the amyloid nanotubes with ordered arrays of imidazoles were used as hydrolase mimic. The SOX‐hemin amyloid nanohybrids featuring a single extant enzyme could integrate different logic networks to access complex digital designs with the help of three concatenated AND gates and biologically relevant stimuli as inputs.     

Alkali-metal hexamethyldisilazide initiated polymerization on alpha-amino acid N-substituted N-carboxyanhydrides for facile polypeptoid synthesis

Polypeptoids have been explored as mimics of polypeptides,owing to polypeptoids' superior stability upon proteolysis.Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides(NNCAs).However,the speed of polymerization of NNCAs can be ve ry slow,especially for NNCAs bearing a bulky N-substitution group.This hindered the explo ration on polypeptoids with more diverse structures and functions.Therefore,it is in great need to develop advanced strategies that can accelerate the polymerization on inactive NNCAs.Hereby,we report that lithium/sodium/potassium hexamethyldisilazide(Li/Na/KHMDS) initiates a substantially faster polymerization on NNCAs than do commonly used amine initiators,especially for NNCAs with bulky Nsubstitution group.This fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides.     

Porphyrin–BODIPY-based hybrid model compounds for artificial photosynthetic reaction centers

In this review, we report the synthesis and photophysical studies of porphyrin–4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) compounds linked either with different covalent bonds or with axial coordination to metalloporphyrin. BODIPY moiety significantly increases the light absorption capability of porphyrins by efficient BODIPY to porphyrin excitation energy transfer. The type of linkage between the two chromophores significantly affects the energy transfer efficiency. The most efficient energy transfer was proved for compounds linked via a cyanuric chloride bridge (∼99% quenching). Therefore, this type of bond seems to be more appropriate choice in constructing porphyrin–BODIPY assemblies for light harvesting applications. Moreover, the functionalization of the conjugates with fullerenes appears to be interesting electron transfer dynamics in the excited state.     

Robust synthesis of enantiopure cyclohexenyl analogues of 2/3-deoxyribose sugars as carbocyclic nucleoside precursors

An expedient synthesis of 2-deoxy (10) and 3-deoxy (11) cyclohexenyl analogues of 2-deoxy and 3-deoxy-d-ribose sugar from commercially available starting materials is reported. Highly efficient enzymatic resolution of the key compound 10 is described using lipase under hydrolytic conditions. The robust methodology applied here will be useful to synthesize cyclohexenyl nucleosides, which possess potent antiviral activity and are capable of gene silencing via RNAi or antisense applications.     

Enzyme mimics based upon supramolecular coordination chemistry

Recent advances in supramolecular coordination chemistry have allowed chemists to synthesize macromolecular complexes that exhibit various properties intrinsic to enzymes. This Review focuses on structures inspired by properties and functions observed in enzymes rather than precise models of enzyme active sites. These structures are synthesized using convergent, modular, and high-yielding coordination-chemistry-based methods, which allow one to tailor the size, shape, and properties of the resulting complexes. Many of the structures discussed exhibit reactivity and specificity reminiscent of natural systems, and some of them have functions that exceed the natural systems which provided the inspiration for initially making them.     

Disproportionation of H2O2 Mediated by Diiron-Peroxo Complexes as Catalase Mimics

Heme iron and nonheme dimanganese catalases protect biological systems against oxidative damage caused by hydrogen peroxide. Rubrerythrins are ferritine-like nonheme diiron proteins, which are structurally and mechanistically distinct from the heme-type catalase but similar to a dimanganese KatB enzyme. In order to gain more insight into the mechanism of this curious enzyme reaction, non-heme structural and functional models were carried out by the use of mononuclear [Fe^II(L_1–4)(solvent)₃](ClO₄)₂ (1–4) (L₁ = 1,3-bis(2-pyridyl-imino)isoindoline, L₂ = 1,3-bis(4′-methyl-2-pyridyl-imino)isoindoline, L₃ = 1,3-bis(4′-Chloro-2-pyridyl-imino)isoindoline, L₄ = 1,3-bis(5′-chloro-2-pyridyl-imino)isoindoline) complexes as catalysts, where the possible reactive intermediates, diiron-perroxo [Fe^III₂(μ-O)(μ-1,2-O₂)(L₁-L₄)₂(Solv)₂]²⁺ (5–8) complexes are known and well-characterized. All the complexes displayed catalase-like activity, which provided clear evidence for the formation of diiron-peroxo species during the catalytic cycle. We also found that the fine-tuning of iron redox states is a critical issue, both the formation rate and the reactivity of the diiron-peroxo species showed linear correlation with the Fe^III/Fe^II redox potentials. Their stability and reactivity towards H₂O₂ was also investigated and based on kinetic and mechanistic studies a plausible mechanism, including a rate-determining hydrogen atom transfer between the H₂O₂ and diiron-peroxo species, was proposed. The present results provide one of the first examples of a nonheme diiron-peroxo complex, which shows a catalase-like reaction.     

分子印迹微凝胶模拟酶的研究

采用油包水反相乳液法, 以马来酸酐酯化葡聚糖-氨基吡啶偶联物(Dex-MA-AP)为功能大单体、过渡态类似物p-硝基苯磷酸酯(NPP)为模板分子、Co2+为中心离子, 制得分子印迹微凝胶模拟酶(MIGs). 用紫外光谱研究了Dex-MA-AP上吡啶功能基团与NPP之间的相互作用. 用SEM观察了MIGs的形貌和大小. 研究发现, MIGs催化活性受模板分子和交联剂用量的影响,MIGs催化p-硝基乙酸苯酯(NPA)水解反应行为可用Michaelis-Menten方程进行描述, 其最大催化水解反应速率(Vm)和Michaelis-Menten常数(Km)分别为25.1 nmol/h和0.030 mmol/L, 且具有较好的催化选择性.