Dehydroalanine (Dha) and dehydrobutyrine (Dhb) are remarkably versatile non‐canonical amino acids often found in antimicrobial peptides. This work presents the selective modification of Dha and Dhb in antimicrobial peptides through photocatalytic activation of organoborates under the influence of visible light. Ir(dF(CF3)ppy)2(dtbbpy)PF6 was used as a photoredox catalyst in aqueous solutions for the modification of thiostrepton and nisin. The mild conditions and high selectivity for the dehydrated residues show that photoredox catalysis is a promising tool for the modification of peptide‐derived natural products.

Dehydroalanine (Dha) is a remarkably versatile non‐canonical amino acid often found in antimicrobial peptides. Herein, we present the catalytic modification of Dha by a palladium‐mediated cross‐coupling reaction. By using Pd(EDTA)(OAc)2 as water‐soluble catalyst, a variety of arylboronic acids was coupled to the dehydrated residues in proteins and peptides, such as Nisin. The cross‐coupling reaction gave both the Heck product, in which the sp2‐hybridisation of the α‐carbon is retained, as well as the conjugated addition product. The reaction can be performed under mild aqueous conditions, which makes this method an attractive addition to the palette of bio‐orthogonal catalytic methods.

No abstract

Dehydroalanine (Dha) residues are attractiven oncanonical amino acids that occur naturallyi nr ibosomally synthesised and post-translationallym odifiedp eptides (RiPPs).D ha residues are attractive targets for selective latestage modificationo ft hese complex biomolecules. In this work, we show the selective photocatalytic modification of dehydroalanine residues in the antimicrobialp eptiden isin and in the proteins small ubiquitin-likem odifier (SUMO) and superfolder green fluorescent protein (sfGFP). For this purpose, an ew water-soluble iridium(III) photoredox catalyst was used. Thed esign and synthesis of this new photocata-lyst, [Ir(dF(CF 3)ppy) 2 (dNMe 3 bpy)]Cl 3 ,i sp resented. In contrast to commonlyu sed iridium photocatalysts, this complex is highlyw ater soluble and allows peptides and proteins to be modified in water and aqueous solvents under physiologically relevant conditions, with short reaction times and with low reagent and catalystl oadings.T his work suggestst hat photoredox catalysis using this newly designed catalysti sa promising strategy to modify dehydroalanine-containing natural products and thus could have great potentialf or novelb ioconjugation strategies.

The cytotoxicity of the anti-tumor drug BLM is believed to be related to the ability of the corresponding iron complex (Fe-BLM) to engage in oxidative double-strand DNA cleavage. The iron complex of the ligand N4Py (Fe-N4Py; N4Py = N,N-bis(2-pyridyl)-N-bis(2-pyridyl)methylamine) has proven to be a particularly valuable spectroscopic and functional model for Fe-BLM. It is also a very active oxidative DNA-cleaving agent. However, like all other synthetic Fe-BLM mimics, it gives only single-strand DNA cleavage. Since double-strand DNA cleavage requires the delivery of two oxidizing equivalents to the DNA, it was envisaged that multinuclear iron complexes might be capable of effecting double-strand cleavage. For this purpose, a series of ditopic and tritopic N4Py-derived ligands has been synthesized and the corresponding iron complexes have been evaluated for their efficacy in the oxidative cleavage of supercoiled pUC18 plasmid DNA. The dinuclear iron complexes showed significantly enhanced double-strand cleavage activity compared to mononuclear Fe-N4Py, which was relatively independent of the structure of the linking moiety. Covalent attachment of a 9-aminoacridine intercalator to a dinuclear complex did not give rise to improved double-strand DNA cleavage. The most efficient oxidative double-strand cleavage agents proved to be the trinuclear iron complexes. This is presumably the result of increased probability of the simultaneous delivery of two oxidizing equivalents to the DNA.

The site-specific incorporation of transition-metal complexes within DNA duplexes, followed by their immobilization on a gold surface, was studied by electrochemistry to characterize their ability to mediate charge. Cyclic voltammetry, square-wave voltammetry, and control experiments were carried out on fully matched and mismatched DNA strands that are mono- or bis-labeled with transition-metal complexes. These experiments are all consistent with the ability of the metal centers to act as a redox probe that is well coupled to the DNA π-stack, allowing DNA-mediated charge transport.