Engineering Dendritic Aptamer Assemblies as Superior Inhibitors of Protein Function

Abstract

Copper‐catalyzed aerobic coupling of thiols and alcohols affords sulfinates and thiosulfonates. These products are assumed to form via sulfinyl radicals which are not commonly found in oxidative coupling reactions of thiols. A reaction mechanism involving sulfinyl radicals is proposed, and mass and electron paramagnetic resonance (EPR) experimental results are provided.

Aptamers as targeted therapeutics: current potential and challenges

“…When non-formulated aptamers are administered into the blood stream, even using stabilizing backbone modifications, small aptamers are subject to rapid excretion through renal filtration. To overcome renal filtration and extend circulation time, aptamers are generally formulated with a bulky moiety, such as high molecular mass PEG 69 , cholesterol 79, 80 , proteins 81, 82 , liposomes 83 , organic or inorganic nanomaterials 10, 84 , or are multimerized 85–87 to create a multivalent molecule above the cutoff threshold for the renal glomerulus (30–50 kDa). PEG is a well-studied, hydrophilic biomaterial which decreases aggregation and increases solubility of the conjugates.…”

Self‐Assembled Aptamer‐Based Drug Carriers for Bispecific Cytotoxicity to Cancer Cells

“…To develop bi-or trispecific aptamer-based drug carriers, we first constructed bi-and trispecific aptamers (multiaptamers) and studied their recognition capabilities. Engineering multiaptamers is similar to multivalency engineering, which has been previously reported for antibodies [11] and aptamers, [12] by using chemical linkages or nanomaterials for binding affinity improvement, targeted therapy, cell-cell interactions, and so forth. In this study, chemical linkages were used.…”

“…Engineering multi-aptamers is similar to multivalency engineering, which has been previously reported for antibodies [11] and aptamers [12] using chemical linkages or nanomaterials for binding affinity improvement, targeted therapy, cell-cell interaction, etc. In this study, chemical linkages were used.…”

Polyvalent nucleic acid aptamers and modulation of their activity: a focus on the thrombin binding aptamer

“…In another approach, a heterogeneous thrombin ligand composed of TBA 15 and TBA 27 aptamers incorporated into dendritic assembly was developed, which provided further improvement in the inhibitory efficacy (Kim et al, 2010). In particular, the assembly was composed of three functional groups: 1) the TBA 27 aptamer, that possesses high binding affinity to thrombin, 2) the dendritic part composed of multiple TBA 15 aptamers with the specific enzymatic inhibitory functions required for thrombin-mediated coagulation, and 3) polyethylene glycol linkers, optimized in length, that chemically link the dendritic part to the TBA 27 .…”