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Bioconjugate chemistry is the study of linking one molecule to another by chemical or biological means. The resulting complexes will typically be formed from at least one biomolecule, though they can also be purely synthetic molecules with a biological application.
Approved antibody–drug conjugates (ADCs) remain constrained by a limited repertoire of payloads with restricted modes of action. Here, the authors present phosphoramidate-based self-immolative linker units that facilitate stable attachment in serum and traceless drug release in the target cell from aliphatic and aromatic alcohols with various modes of action.
While fluorophore-biomacromolecule systems are relatively well known, afterglow luminophore-biomacromolecule conjugates/complexes are rarely studied. Here, the authors report the development of a system with organic afterglow from luminophore-protein conjugates/complexes at freezing temperatures.
Fundamental biophysical principles that govern particle inclusion in or exclusion from condensates are discovered, wherein arbitrarily large particles controllably partition into condensates given sufficiently strong condensate-particle interactions.
Covalent inhibitors are a successful class of drugs, however, the optimization of targeted covalent inhibitors has challenges due to the need to increase non-covalent interactions and modulate reactivity. Here, the authors study the structure-reactivity-activity relationships of analogues of the EGFR inhibitor poziotinib, showing practical methods to characterize structure-activity relationships, providing insights into the origins of potency and highlighting the effect of chirality on covalent binding.
Developing effective inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) is challenging because of the enzyme’s shallow catalytic pocket and non-specific substrate binding interactions. Here, the authors use Sulfur (VI) fluoride exchange chemistries to prepare covalent TDP1-bound binders showing site-specific covalent bonds with the Y204 residue that position DNA.
Antibody–drug conjugates (ADCs) are promising targeted cancer therapies but have a limited payload scope. Antibody–bottlebrush prodrug conjugates offer modular synthesis and high drug-to-antibody ratios, enabling the use of a broad range of payloads, including lower potency drugs, while performing favorably compared to traditional ADCs in preclinical models.
Direct C–H selenylation of biomacromolecules under biocompatible conditions has long posed a formidable challenge. Now, engineered selenoxide reagents have been shown to achieve site-specific incorporation of selenium into DNA and proteins within physiologically relevant environments.
Ribosomes have now been shown to accept certain initiator tRNAs acylated with aromatic foldamer–dipeptides thereby enabling the translation of a peptide or protein with a short aromatic foldamer at the N-terminus. Some foldamer–peptide hybrids could be cyclized to generate macrocycles that present conformationally restricted peptide loops.
Protein drugs are important therapies for many different diseases, but very few can be administered orally. Now, a cationic dendronized polymer has been shown to stabilize a therapeutic protein for delivery to the gut.
