Scaling the Amphiphilic Character and Antimicrobial Activity of Gramicidin S by Dihydroxylation or Ketal Formation.

The acid lability of aliphatic ketals, which often serve as protection groups for 1,2-diols, is influenced by their local structural environment. The acetonide of the protected amino acid cis-dihydroxyproline (Dyp) is a typical protecting group cleavable by traces of TFA. The tricyclic acetonide of the dipeptide d-Hot═Tap is resistant to TFA and thus can serve as a bioorthogonal modification of bioactive peptides.

Self-assembly of peptide boroxoles on cis-dihydroxylated oligoamide templates in water.

We develop templates that can be used to stabilize consistent oligomers of a bioactive peptide. In the present study, we synthesize oligomers of an antibody epitope from the amyloidogenic prion protein. Dynamic covalent chemistry is the basis for the spontaneous condensation of 2, 3, 4 or 6 peptides with qualified polyol templates presenting the required number of bioorthogonal ligation sites.

Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines.

New macrocyclic plasmin inhibitors based on our previously optimized P2-P3 core segment have been developed. In the first series, the P4 residue was modified, whereas the 4-amidinobenzylamide in P1 position was maintained. The originally used P4 benzylsulfonyl residue could be replaced by various sulfonyl- or urethane-like protecting groups.

Improved δ-valerolactam templates for the assembly of Aβ-miniamyloids by boronic ester formation.

The 6,7,8,8a-cis (all-cis) substituted δ-valerolactams of type 10, 11 and 12 are high-affinity diols for boronic ester formation, superior to the corresponding 6,7-trans analogues 1, 3 and 4. X-ray and NMR structure analysis have identified the differences of the six-membered ring conformations which cause the improved esterification properties of the all-cis stereoisomers. The homooligomeric all-cisδ-valerolactams 46-48 are used as polyol templates for the self-assembly of peptidic oligomers 49-52 by dynamic covalent chemistry.