The emerging inverse electron demand Diels–Alder (IEDDA) reaction stands out from other
bioorthogonal reactions by virtue of its unmatchable kinetics, excellent orthogonality and …

Proteins constitute the majority of nature's worker biomolecules. Designed for specific
functions, complex tertiary structures make proteins ideal candidates for analysing natural …

Over 500 natural and synthetic amino acids have been genetically encoded in the last two
decades. Incorporating these noncanonical amino acids into proteins enables many …

Reactions that occur under physiological conditions find diverse uses in the chemical and
biological sciences. However, the limitations that biological systems place on chemical …

The use of a bioorthogonal reaction for the selective cleavage of tumor-bound antibody–
drug conjugates (ADCs) would represent a powerful new tool for ADC therapy, as it would …

The inverse‐electron‐demand Diels–Alder (iDA) reaction has recently been repurposed as
a bioorthogonal decaging reaction by accelerating the elimination process after an initial …

Engineering new functionality into living eukaryotic systems by enzyme evolution or de novo
protein design is a formidable challenge. Cells do not rely exclusively on DNA-based …

Abstract Inverse electron demand Diels–Alder reactions between s‐tetrazines and strained
dienophiles have numerous applications in fluorescent labeling of biomolecules. Herein, we …

The strain‐promoted alkyne‐azide cycloaddition (SPAAC) is the most commonly employed
bioorthogonal reaction with applications in a broad range of fields. Over the years, several …

Bioorthogonal chemistry holds great potential to generate difficult‐to‐access protein–protein
conjugate architectures. Current applications are hampered by challenging protein …