Selection of aptamers from oligonucleotide libraries currently requires multiple rounds of alternating steps of partitioning of binders from nonbinders and enzymatic amplification of all collected oligonucleotides.H erein, we report ahighly practical solution for reliable one-step selection of aptamers.W eintroduce partitioning by ideal-filter capillary electrophoresis (IFCE) in whichbinders and nonbinders move in the opposite directions.T he efficiency of IFCE-based partitioning reaches 10 9 ,w hichi st en million times higher than that of typical solid-phase partitioning methods.One step of IFCE-based partitioning is sufficient for the selection of ah igh-affinity aptamer pool for ap rotein target. Partitioning by IFCE promises to become an indispensable tool for fast and robust selection of binders from different types of oligonucleotide libraries.Aptamers are oligonucleotides that can bind target molecules with high affinity and selectivity; [1] they find avariety of practical applications. [2] Aptamers are typically selected from random-sequence oligonucleotide libraries in ap rocess termed SELEX. [1][2][3] SELEX involves iterated rounds of incubation of the library with the target followed by partitioning of target-binding oligonucleotides (binders) from target-nonbinding oligonucleotides (nonbinders) and PCR amplification of all collected oligonucleotides until the binder-to-nonbinder ratio (B/N)r eaches ad esired value, preferably greater than unity.R emarkably,S ELEX fails to select binders in 70 %o fa ttempts. [4] This multi-round procedure is inherently prone to failure because PCR preferentially amplifies nonbinders,which are less structured oligonucleotides than binders and are,h ence,m ore easily accessible to polymerases. [5] As ar esult, SELEX enriches readily amplifiable nonbinders instead of binders if the efficiency of enriching binders in partitioning is lower than the efficiencyo fe nriching these nonbinders in PCR amplification. [6] An obvious solution to this daunting problem is increasing the efficiency of partitioning to the level at which its single step becomes sufficient for reaching the desired B/N. There have been several reports claiming one-step selection of aptamers. [7] However, neither of the suggested methods has been independently confirmed since their introduction in 2005-2012, thus,questioning at least their transferability and practicality and likely their reliability.H erein, we report on aq uantitatively validated, highly practical, and easily adoptable approach for one-step selection of aptamers.W eh ope that the new approach will be adopted and successfully used by many in the large and diverse in vitro selection community.This work was inspired by our understanding that there are two major reasons for the lack of ar obust and practical way of one-step selection of aptamers.T he first reason is methodological;while high efficiencies of partitioning are the implied goal, they are typically not measured and not used to guide developments or substantiate claims of one-s...

A method for regioselective N-alkylation of ambident, azole-type heterocycles with alkene or epoxide electrophiles is described. In the presence of diphenylborinic acid (Ph2BOH) and an amine cocatalyst, heterocyclic nucleophiles such as 1,2,3- and 1,2,4-triazoles, substituted tetrazoles, and purine are activated toward selective N-functionalization. The scope of electrophilic partners includes enones, 2-vinylpyridine, phenyl vinyl sulfone, a dehydroalanine derivative, and epoxides. Mechanistic studies, including in situ 11B NMR spectroscopy and kinetic analysis, are discussed.

A method for regioselective ring openings of 3,4- and 2,3-epoxy alcohols with ambident nitrogen heterocycles is described. Using a diarylborinic acid catalyst, a single regioisomer is favored in couplings of nucleophile and electrophile partners that display low regioselectivity under conventional conditions. The method provides access to aromatic heterocycles bearing stereochemically defined, functionalized alkyl substituents, a product class similar in structure to medicinally relevant compounds such as the acyclic nucleoside analogues.

Selection of aptamers from oligonucleotide libraries currently requires multiple rounds of alternating steps of partitioning of binders from nonbinders and enzymatic amplification of all collected oligonucleotides. Herein, we report a highly practical solution for reliable one‐step selection of aptamers. We introduce partitioning by ideal‐filter capillary electrophoresis (IFCE) in which binders and nonbinders move in the opposite directions. The efficiency of IFCE‐based partitioning reaches 109, which is ten million times higher than that of typical solid‐phase partitioning methods. One step of IFCE‐based partitioning is sufficient for the selection of a high‐affinity aptamer pool for a protein target. Partitioning by IFCE promises to become an indispensable tool for fast and robust selection of binders from different types of oligonucleotide libraries.