Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• substrate engineering and minimising risks such as aggregation and immunogenicity, and hence site-specific modifications of commonly found surface residues are desired. Tools are also expected to be easy to prepare and apply, yet remain reliably functional in vitro and in vivo settings. The use of harsh

• delivered double variants G250S/E300D (“S2”) and G250S/K327T (“S13”), both capable of generating ADCs with DAR close to 2.0. Second, substrate engineering revealed that MTG preferentially processes positively charged peptides, with an RAK-containing motif supporting efficient ligation to fully glycosylated

• antibodies [150]. Collectively, these enzyme- or substrate-engineering approaches enabled native-state labelling of multiple antibodies (avelumab, matuzumab, cetuximab, and rituximab), producing stable conjugates with favourable biodistribution [149][150]. Another example is the engineering of the hydrolase

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• strategies for controlling reaction pathways and selectivity predominantly involve precise manipulation of catalytic systems (metal catalysts/ligands), reaction parameters (solvent, temperature, time), acid/base mediation, and strategic substrate engineering. This review systematically organizes recent

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• synthesised in amorphadiene synthase-catalysed reactions from 8- and 12-methoxyfarnesyl diphosphates due to the highly plastic yet tightly controlled carbocationic chemistry of this sesquiterpene cyclase. Keywords: artemisinin; amorphadiene synthase; oxygenated terpenoids; sesquiterpenoids; substrate

• engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• ; P450 monooxygenase; substrate engineering; Introduction P450 monooxygenases are a ubiquitous family of enzymes found in a wide variety of organisms in all domains of life. These enzymes catalyse oxidation reactions such as hydroxylation, epoxidation, N- and O-dealkylation and heteroatom oxidation