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.

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.

Convenient methods of preparing aza-dibenzocyclooctynes are disclosed herein. Aza-dibenzocyclooctynes attached to a surface are also disclosed herein. Aza-dibenzocyclooctynes can be reacted with azides to form heterocyclic compounds. Such reactions can be useful in a wide variety of applications including, for example, labeling surfaces.

Convenient methods of preparing aza-dibenzocyclooctynes are disclosed herein. Aza-dibenzocyclooctynes attached to a surface are also disclosed herein. Aza-dibenzocyclooctynes can be reacted with azides to form heterocyclic compounds. Such reactions can be useful in a wide variety of applications including, for example, labeling surfaces.

The disclosure is directed to the synthesis and improved methods for purifying macrocyclic peptides produced by solid phase peptide synthesis. The synthesized peptide is capped with an alkyne-functionalized or azide-functionalized compound of formula (I): ##STR00001##
prior to cleavage of the peptide from the solid phase support.

The disclosure is directed to the synthesis and improved methods for purifying macrocyclic peptides produced by solid phase peptide synthesis. The synthesized peptide is capped with an alkyne-functionalized or azide-functionalized compound of formula (I): ##STR00001##
prior to cleavage of the peptide from the solid phase support.

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.

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 present invention relates to a cycloaddition process comprising the step of reacting a halogenated aliphatic 1,3-dipole compound with a (hetero)cycloalkyne according to Formula (1): Preferably, the (hetero)cycloalkyne according to Formula (1) is a (hetero)cyclooctyne. The invention also relates to the cycloaddition products obtainable by the process according to the invention. The invention further relates to halogenated aliphatic 1,3-dipole compounds, in particular to halogenated aliphatic 1,3-dipole compounds comprising N-acetylgalactosamine-UDP (GalNAc-UDP), and to halogenated 1,3-dipole compounds comprising (peracylated) N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), N-acetylmannosamine (ManNAc) and N-acetyl neuraminic acid (NeuNAc). ##STR00001##

The present invention relates to a cycloaddition process comprising the step of reacting a halogenated aliphatic 1,3-dipole compound with a (hetero)cycloalkyne according to Formula (1): Preferably, the (hetero)cycloalkyne according to Formula (1) is a (hetero)cyclooctyne. The invention also relates to the cycloaddition products obtainable by the process according to the invention. The invention further relates to halogenated aliphatic 1,3-dipole compounds, in particular to halogenated aliphatic 1,3-dipole compounds comprising N-acetylgalactosamine-UDP (GalNAc-UDP), and to halogenated 1,3-dipole compounds comprising (peracylated) N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), N-acetylmannosamine (ManNAc) and N-acetyl neuraminic acid (NeuNAc). ##STR00001##