A growing number of approaches to “staple” α‐helical peptides into a bioactive conformation using cysteine cross‐linking are emerging. Here, the replacement of l‐cysteine with “cysteine analogues” in combinations of different stereochemistry, side chain length and beta‐carbon substitution, is explored to examine the influence that the thiol‐containing residue(s) has on target protein binding affinity in a well‐explored model system, p53–MDM2/MDMX, which is constituted by the interaction of the tumour suppressor protein p53 and proteins MDM2 and MDMX, which regulate p53 activity. In some cases, replacement of one or more l‐cysteine residues afforded significant changes in the measured binding affinity and target selectivity of the peptide. Computationally constructed homology models indicate that some modifications, such as incorporating two d‐cysteine residues, favourably alter the positions of key functional amino acid side chains, which is likely to cause changes in binding affinity, in agreement with measured surface plasmon resonance data.

A combined single-crystal X-ray diffraction and NMR crystallography study of a 1:1 cocrystal of two fungicides, namely di­thia­non and pyrimethanil, is presented. Specifically, the role of hydrogen bonding and C—H⋯π and S⋯O inter­molecular inter­actions is qu­anti­tatively investigated.

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A crystallographic study highlighting the benefits of a combined XRD and NMR approach in investigating both stability and variation within an organic multicomponent crystal.