Evolution of Complex Target SELEX to Identify Aptamers against Mammalian Cell-Surface Antigens

The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This review summarizes these milestones that have pushed the field forward, allowing researchers to generate aptamers that can potentially be applied as therapeutic and diagnostic agents

Tribromo(3,5-dimethyl-2-nitrophenyl-j2 C1 ,O)tellurium(IV), bromo(3,5-dimethyl-2-nitrophenyl-j2 C1 ,O)tellurium(II) and bromo(3,5-dimethyl-2-nitrosophenyl-j2 C1 ,O)tellurium(II)

All three title compounds, prepared from bis(3,5-dimethyl-2- nitrophenyl)ditellurium, exhibit high degrees of intramolecular TeÐO coordination. Their TeÐO distances increase in the order C8H8BrNOTe \u3c C8H8BrNO2Te \u3c C8H8Br3NO2Te, with distances of 2.165 (3), 2.306 (1) and 2.423 (6) AÊ , respectively, indicating that C8H8BrNOTe may be more aptly described as 1-bromo-4,6-dimethyl-2,1,3-benzoxatellurazole

(μ-Diazenediyldiphenyl-κ2C2, N2: κ2C2′, N1) bis [(3, 5-dimethylphenyl) tellurium (II)].

The title compound, C28H26N2Te2, prepared by reduction of (3,5-dimethylphenyl)(2-nitrophenyl)tellurium(II), is the first structurally characterized example of an azo group bridging two TeII centers. The compound is centrosymmetric and the Te—N distance [2.6916 (19) A ° ] is longer than in non-bridging azo compounds

A multivalent DNA aptamer specific for the B-cell receptor on human lymphoma and leukemia

Long-term survival still eludes most patients with leukemia and non-Hodgkin’s lymphoma. No approved therapies target the hallmark of the B cell, its mIgM, also known as the B-cell receptor (BCR). Aptamers are small oligonucleotides that can specifically bind to a wide range of target molecules and offer some advantages over antibodies as therapeutic agents. Here, we report the rational engineering of aptamer TD05 into multimeric forms reactive with the BCR that may be useful in biomedical applications. Systematic truncation of TD05 coupled with modification with locked nucleic acids (LNA) increased conformational stability and nuclease resistance. Trimeric and tetrameric versions with optimized polyethyleneglycol (PEG) linker lengths exhibited high avidity at physiological temperatures both in vitro and in vivo. Competition and protease studies showed that the multimeric, optimized aptamer bound to membrane-associated human mIgM, but not with soluble IgM in plasma, allowing the possibility of targeting leukemias and lymphomas in vivo. The B-cell specificity of the multivalent aptamer was confirmed on lymphoma cell lines and fresh clinical leukemia samples. The chemically engineered aptamers, with significantly improved kinetic and biochemical features, unique specificity and desirable pharmacological properties, may be useful in biomedical applications