Syntheses and structures of piperazin-1-ium ABr2 (A = Cs or Rb): hybrid solids containing 'curtain wall' layers of face- and edge-sharing ABr6 trigonal prisms.

The isostructural title compounds, poly[piperazin-1-ium [di-µ-bromido-caesium]], {(C4H11N2)[CsBr2]} n , and poly[piperazin-1-ium [di-µ-bromido-rubidium]], {(C4H11N2)[RbBr2]} n , contain singly-protonated piperazin-1-ium cations and unusual ABr6 (A = Cs or Rb) trigonal prisms. The prisms are linked into a distinctive 'curtain wall' arrangement propagating in the (010) plane by face and edge sharing. In each case, a network of N-H⋯N, N-H⋯Br and N-H⋯(Br,Br) hydrogen bonds consolidates the structure.

Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants.

Macrocyclic peptides have promising therapeutic potential but the scaling up of their chemical synthesis is challenging. The cyanobactin macrocyclase PatGmac is an efficient tool for production but is limited to substrates containing 6-11 amino acids and at least one thiazoline or proline. Here we report a new cyanobactin macrocyclase that can cyclize longer peptide substrates and those not containing proline/thiazoline and thus allows exploring a wider chemical diversity.

A Blind Test of Computational Technique for Predicting the Likelihood of Peptide Sequences to Cyclize.

An in silico computational technique for predicting peptide sequences that can be cyclized by cyanobactin macrocyclases, e.g., PatGmac, is reported. We demonstrate that the propensity for PatGmac-mediated cyclization correlates strongly with the free energy of the so-called pre-cyclization conformation (PCC), which is a fold where the cyclizing sequence C and N termini are in close proximity. This conclusion is driven by comparison of the predictions of boxed molecular dynamics (BXD) with experimental data, which have achieved an accuracy of 84%. A true blind test rather than training of the model is reported here as the in silico tool was developed before any experimental data was given, and no parameters of computations were adjusted to fit the data. The success of the blind test provides fundamental understanding of the molecular mechanism of cyclization by cyanobactin macrocyclases, suggesting that formation of PCC is the rate-determining step. PCC formation might also play a part in other processes of cyclic peptides production and on the practical side the suggested tool might become useful for finding cyclizable peptide sequences in general.