Organic compounds for target identification, drug discovery, chemical library production, high-throughput screening, fluorophore conjugation, chemiluminescent compound conjugation, creation of proximity induced modulators (e.g., protein degraders)/chimeric molecules, or a combination thereof are described. The compounds can contain small molecule moieties for identification of their potential targets; an isocyanate, photoactivatable groups; chemical moieties for enrichment and detection of target-small molecule moiety interactions; proximity induced modulator element; fluorophores; chemiluminescent groups; or combinations thereof.

The invention is directed to methods for synthesizing oligonucleotides directly on biomolecules or cells living or fixed. In some embodiments, template-free enzymatic synthesis is implemented under biological conditions with successive cycles of (i) enzymatic addition of a 3′-O-blocked nucleoside triphosphate and (ii) enzymatic deblocking of the incorporated nucleotide to regenerate a free 3′ hydroxyl. The invention has applications in single-cell cDNA library construction and analysis.

The invention is directed to methods for synthesizing oligonucleotides directly on biomolecules or cells living or fixed. In some embodiments, template-free enzymatic synthesis is implemented under biological conditions with successive cycles of (i) enzymatic addition of a 3′-O-blocked nucleoside triphosphate and (ii) enzymatic deblocking of the incorporated nucleotide to regenerate a free 3′ hydroxyl. The invention has applications in single-cell cDNA library construction and analysis.

Solid-phase synthesis of a peptide has a problem that a desired elongation reaction is prevented from proceeding by diketopiperazine and a 6-membered diamine skeleton compound formed when a protective group at the N-terminal is removed. The present inventors have found that when in production of a peptide by a solid-phase method, a peptide in which an amino group at the N-terminal is protected with a protective group having an Fmoc skeleton is treated in a specific solvent with a base having a pKa of 23 or more in acetonitrile as a conjugate acid, and a peptide chain is then elongated, it is possible to solve the problem described above.

Solid-phase synthesis of a peptide has a problem that a desired elongation reaction is prevented from proceeding by diketopiperazine and a 6-membered diamine skeleton compound formed when a protective group at the N-terminal is removed. The present inventors have found that when in production of a peptide by a solid-phase method, a peptide in which an amino group at the N-terminal is protected with a protective group having an Fmoc skeleton is treated in a specific solvent with a base having a pKa of 23 or more in acetonitrile as a conjugate acid, and a peptide chain is then elongated, it is possible to solve the problem described above.

A method for identification of the most abundant oligonucleotide species in a library of oligonucleotides comprising more than 10.sup.6 oligonucleotide species, wherein the oligonucleotides of the library of oligonucleotides are not inherently capable of exponential amplification by PCR and include a coding sequence, which is characteristic of one oligonucleotide specie of the library of oligonucleotides and only one fixed sequence, which is present in a plurality of oligonucleotide species of the library of oligonucleotides, said fixed sequence being located on a 5′ side of the coding sequence, and wherein the method comprises specifically amplifying the sequence of a hybridised oligonucleotide species using the steps of: incubating the library of oligonucleotides under conditions of hybridization such as to allow complementary coding sequences to hybridize and form hybridized oligonucleotide species; extending a 3′ end of one or more of the hybridised oligonucleotide species, having only one fixed sequence, to provide extended sequences having an extended region, such that the extended region generates a second fixed sequence thereby forming extended sequences having two fixed sequences; amplifying extended sequences comprising two fixed sequences using PCR to provide amplified sequences, and optionally identifying an identity of the amplified sequences thereby revealing an identity of the hybridised oligonucleotide species in the step of incubating. The library of oligonucleotides is selected from the group of a library of encoded molecules, a library of aptamers, a library of reporter sequences derived from a library of encoded molecules, and a library of aptamers.

Methods and devices are provided for preparing a protein array having a plurality of proteins. In one embodiment, the method includes providing a plurality of nucleic acids each having a predefined sequence and expressing in vitro a plurality of proteins from the plurality of nucleic acids. In another embodiment, protein arrays having a solid surface and a microvolume are also provided. The solid surface can have a plurality of anchor oligonucleotides capable of hybridizing with a plurality of nucleic acids. The microvolume can cover each of the plurality of anchor oligonucleotides and can be configured to produce a polypeptide from each of the plurality of nucleic acids.

Methods and devices are provided for preparing a protein array having a plurality of proteins. In one embodiment, the method includes providing a plurality of nucleic acids each having a predefined sequence and expressing in vitro a plurality of proteins from the plurality of nucleic acids. In another embodiment, protein arrays having a solid surface and a microvolume are also provided. The solid surface can have a plurality of anchor oligonucleotides capable of hybridizing with a plurality of nucleic acids. The microvolume can cover each of the plurality of anchor oligonucleotides and can be configured to produce a polypeptide from each of the plurality of nucleic acids.

Presented are methods and compositions for using immobilized transposase and a transposon end for generating an immobilized library of 5′-tagged double-stranded target DNA on a surface. The methods are useful for generating 5′- and 3′-tagged DNA fragments for use in a variety of processes, including massively parallel DNA sequencing.

Devices, systems and methods for affinity reagent and catalyst discovery employing a library on a bead HTS platform, each bead comprising affixed non-natural polymers of a distinct bioactive monomer with sequence pre-defined branching and folding in tertiary structures, and fiber-optic array scanning technology.