Hepatic stability is crucial for achieving oral bioavailability, as drugs rapidly metabolised by the liver fail to reach effective blood concentrations. This study evaluated the rat liver microsomal stability of N-methylated cyclic hexapeptides. Despite similar sequences, large differences in stability emerged. Poor stability correlated strongly with the presence of cis-amide bonds. NMR and modelling confirmed that cis geometry exposes N-methyl groups to enzymatic attack. These findings identify a cis-amide bond as a key metabolic liability in cyclic peptide drug design. (Image credit: Huy Hoang and Timothy Hill.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

Recent advances in the development of Co₃O₄-based catalysts for acidic oxygen evolution reaction (OER) are reviewed, highlighting structural, electronic and design strategies to enhance activity and stability for practical proton exchange membrane (PEM) water electrolysis applications. Co₃O₄ is a promising non-precious alternative to noble metals like IrO₂ and RuO₂, but long-term stability remains a challenge. The review emphasises key engineering techniques, such as doping, surface modification and defect engineering, to enhance performance for large-scale PEM application. (Image credit: Huihui Li.)

This article belongs to the collection: 2024–25 RACI and AAS Award papers.

This communication reports an iterative one-pot native chemical ligation–desulfurisation method using 7-diethylamino-3-methyl coumarin (DEAMC) as a cysteine protecting group. Selective desulfurisation is conducted in the presence of DEAMC-protected cysteine, enabling subsequent photodeprotection and ligation without purification. The utility of this strategy was demonstrated by the efficient one-pot synthesis of a 60-residue mucin-1 peptide. (Image credit: Lucas Kambanis.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

Palladium and nickel-catalysed cross-coupling reactions are widely used in organic synthesis. Subtle differences in reactivity lead to each metal having advantages and disadvantages, and harnessing the unique properties of each requires a comprehensive mechanistic understanding. This review collates key insights on the transmetalation step of typical cross-coupling reactions. (Image credit: Nicholas S. D. Solomon and Sinead T. Keaveney.)

This article belongs to the collection: 2024–25 RACI and AAS Award papers.

Flavones are natural molecules found in many plants and are known for their potential health benefits, including antioxidant and anticancer properties. In this work, a simple one-step method was developed to make flavones efficiently from readily available starting materials. This streamlined approach makes flavone synthesis more practical and could help accelerate research into new medicines and natural product applications. (Image credit: Khalid Widyan.)

This review highlights ribosomally synthesised and post-translationally modified peptides (RiPPs) from sponges and their microsymbionts. It covers sponge-derived RiPPs, including asteropine A, asteropsins, barrettides, aculeines, stylissamides, recifin A, neopetrosiamides and halichondamide A, as well as RiPPs isolated from sponge microsymbionts, such as polytheonamides, lanthipeptides and thiopeptides. Finally, the review summarises current analytical and genomic tools for RiPP identification and emphasises future perspectives for exploring their ecological and pharmaceutical potential. (Image credit: Sunithi Gunasekera, Jayani Gamage and Paco Cárdenas.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

The solution structure and topology of a pH-sensitive, histidine-rich analogue of the antimicrobial peptide maculatin 1.1 were investigated using circular dichroism, solution-state NMR spectroscopy and molecular dynamics simulations. The peptide conformation transitioned from unstructured in buffer to a straight water-exposed or more buried bent α-helix in DPC micelles at pH 5 or 7 respectively. (Image credit: Marc-Antoine Sani.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

Constrained peptides and compact proteins are exciting amino acid-based molecules with strong potential as new medicines. Smaller than antibodies, they can bind protein surfaces that classical small-molecule drugs struggle to engage. Recent studies using large libraries, rational design and computational tools have produced promising drug candidates. (Image credit: Sven Ullrich.)

This article belongs to the collection: 2024–25 RACI and AAS Award papers.