The large number of emerging antibody-drug conjugates (ADCs) for cancer therapy has resulted in a significant market ‘boom’, garnering worldwide attention. Despite ADCs presenting huge challenges to researchers, particularly regarding the identification of a suitable combination of antibody, linker, and payload, as of September 2021, 11 ADCs have been granted FDA approval, with eight of these approved since 2017 alone. Optimism for this therapeutic approach is clear, despite the COVID-19 pandemic, 2020 was a landmark year for deals and partnerships in the ADC arena, suggesting that there remains significant interest from Big Pharma. Herein we review the enthusiasm for ADCs by focusing on the features of those approved by the FDA, and offer some thoughts as to where the field is headed.

A simple and efficient procedure for the synthesis of substituted benzimidazoles through a one-pot condensation of o-phenylenediamines with aryl aldehydes in the presence of H 2 O 2 /HCl system in acetonitrile at room temperature is described. Short reaction time, large-scale synthesis, easy and quick isolation of the products, and excellent yields are the main advantages of this procedure.

The first total synthesis of the postulated structure of the aminolipopeptide trichoderin A and its epimer are reported. A late-stage solution phase C-terminal coupling was employed to introduce the C-terminal aminoalcohol moiety. This methodology provides a foundation to prepare analogues of trichoderin A to establish a structure-activity relationship. NMR spectroscopic analysis established that the C-6 position of the 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (AHMOD) residue in trichoderin A possesses an (R)-configuration as opposed to the originally proposed (S)-configuration.

Thiol–ene chemistry, a tailored approach to access novel peptide-based drugs.

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The first total synthesis of the highly N-methylated acetylene-containing lipopeptide jahanyne, an apoptosis-inducing natural product from marine cyanobacteria, is reported. A late-stage solution-phase coupling enabled introduction of the C-terminal ketone pyrrolidine moiety. A modified Fmoc solid-phase synthesis strategy was adopted to effectively couple multiple sterically hindered N-methylated amino acids while suppressing epimerization. The total synthesis has enabled confirmation of the proposed absolute configuration of natural jahanyne.

Increased water solubility and long-range intermolecular ordering have been introduced into the fluorescent organic molecule thiophene-diketopyrrolopyrrole via its conjugation to the octapeptide HEFISTAH, derived from a protein–protein β-interface.

We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) technology.