Specific N-terminal attachment of TMTHSI linkers to native peptides and proteins for strain-promoted azide alkyne cycloaddition

The site specific attachment of the reactive TMTHSI-click handle to the N-terminus of peptides and proteins is described. The resulting molecular constructs can be used in strain-promoted azide alkyne cycloaddition (SPAAC) for reaction with azide containing proteins e.g., antibodies, peptides, nanoparticles, fluorescent dyes, chelators for radioactive isotopes and SPR-chips etc.The N-terminal specific attachment of the reactive TMTHSI-click handle to peptides and proteins is described followed by strain-promoted cycloaddition with azide containing peptides, proteins, nucleic acids, or other small or large azide compounds.