Described herein is an enzyme-mediated approach to bioconjugation at nanoparticle (NP) surfaces. This process is enabled by a new synthetic linker compatible with the covalent attachment of alkyne modified substrates, including dyes, peptides and nucleic acids. The methods described herein specifically allow for the linkage of molecules to a DNA-functionalized nanoparticle surface. Enzymatic ligation of molecules to the terminal hydroxyl group of DNA using T4 DNA ligase is achieved through incorporation of a single monophosphate on the approaching substrate. In contrast to previous strategies, the linkers disclosed herein are compatible with alkyne modified molecules of a variety of sizes and charges indicating that the ligase minimally requires the monophosphate and the incoming hydroxyl for conjugation to be successful.

A composition and method for controlled in vitro fragmentation of nucleic acids. A transposase forms catalytically active complexes with a modified transposon end that contains within its end sequence degenerate, apurinic/apyrimidinic sites, nicks, or nucleotide gaps, to fragment or shear a target nucleic acid sample in a controlled process. This method yields desired average nucleic acid fragment sizes. The inventive composition and method may be applied for generation of DNA fragments containing shortened transposon end sequences to facilitate subsequent reactions, for production of asymmetrically tailed DNA fragments, etc.

The invention relates to the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. In another aspect, the invention relates to compounds of formula (II):

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processes for making these compounds, and the use thereof in the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. The invention also relates to methods of synthesis of oligomers, including but not limited to oligopeptides, oligosaccharides and oligonucleotides, particularly oligoribonucleotides and also oligodeoxyribonucleotides, in solution systems, and ionic tag linkers for use in methods provided herein.

The invention relates to the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. In another aspect, the invention relates to compounds of formula (II):

##STR00001##

processes for making these compounds, and the use thereof in the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. The invention also relates to methods of synthesis of oligomers, including but not limited to oligopeptides, oligosaccharides and oligonucleotides, particularly oligoribonucleotides and also oligodeoxyribonucleotides, in solution systems, and ionic tag linkers for use in methods provided herein.

Described herein is an enzyme-mediated approach to bioconjugation at nanoparticle (NP) surfaces. This process is enabled by a new synthetic linker compatible with the covalent attachment of alkyne modified substrates, including dyes, peptides and nucleic acids. The methods described herein specifically allow for the linkage of molecules to a DNA-functionalized nanoparticle surface. Enzymatic ligation of molecules to the terminal hydroxyl group of DNA using T4 DNA ligase is achieved through incorporation of a single monophosphate on the approaching substrate. In contrast to previous strategies, the linkers disclosed herein are compatible with alkyne modified molecules of a variety of sizes and charges indicating that the ligase minimally requires the monophosphate and the incoming hydroxyl for conjugation to be successful.

The invention pertains to construction of next-generation DNA sequencing (NGS) libraries for whole genome sequencing, targeted resequencing, sequencing-based screening assays, metagenomics, or any other application requiring sample preparation for NGS.

The invention relates to a cyclic compound library and a method for making cyclic compounds. The method includes reacting a solid-phase carrier, a molecule containing a photocleavable group, a linking molecule, a building block, and an A-end ring-closure molecule and a B-end ring-closure molecule at the two ends for synthesizing. The method also includes removing the solid-phase carrier using decomposition under light radiation and performing a ring-closure reaction using amino acid residue structures of the A-end ring-closure molecule A and the B-end ring-closure molecule B under the action of a cyclic peptide synthetase.

The invention relates to a cyclic compound library and a method for making cyclic compounds. The method includes reacting a solid-phase carrier, a molecule containing a photocleavable group, a linking molecule, a building block, and an A-end ring-closure molecule and a B-end ring-closure molecule at the two ends for synthesizing. The method also includes removing the solid-phase carrier using decomposition under light radiation and performing a ring-closure reaction using amino acid residue structures of the A-end ring-closure molecule A and the B-end ring-closure molecule B under the action of a cyclic peptide synthetase.

Rapid methods, capable of being performed in a single reaction tube, are described herein for constructing libraries for high-throughput polynucleotide sequencing applications, such as next generation sequencing (NGS) applications. Oligonucleotide probes include chemically-active groups at their 5 or 3 ends, or both, to facilitate the cleavage of their 5 or 3 ends, or both, following their hybridization to the single-stranded ends of frayed template fragments. Cleavage of probe ends reveal single-stranded regions at the ends of the hybridized fragments. Adaptors, specific to these ends, are ligated to the hybridized probe/template fragments, and blunt end fragments are ligated to blunt ends of hybridized probe/template fragments, if present, to generate the adaptor-ligated fragments of the library.

Rapid methods, capable of being performed in a single reaction tube, are described herein for constructing libraries for high-throughput polynucleotide sequencing applications, such as next generation sequencing (NGS) applications. Oligonucleotide probes include chemically-active groups at their 5 or 3 ends, or both, to facilitate the cleavage of their 5 or 3 ends, or both, following their hybridization to the single-stranded ends of frayed template fragments. Cleavage of probe ends reveal single-stranded regions at the ends of the hybridized fragments. Adaptors, specific to these ends, are ligated to the hybridized probe/template fragments, and blunt end fragments are ligated to blunt ends of hybridized probe/template fragments, if present, to generate the adaptor-ligated fragments of the library.