Cell-Permeable Peptide Inhibitors of the p53-hDM2 Interaction via Foldamer Helix Mimicry and Bis-Thioether Stapling.

Combining helical foldamers with α-peptides can produce α-helix mimetics with a reduced peptide character and enhanced resistance to proteolysis. Previously, we engineered a hybrid peptide-oligourea sequence replicating the N-terminal α-helical domain of p53 to achieve high affinity binding to hDM2. Here, we further advance this strategy by combining the foldamer approach with side chain cross-linking to create more constrained cell-permeable inhibitors capable of effectively engaging the target within cells.

Guanidinium-Stapled Helical Peptides for Targeting Protein-Protein Interactions.

Peptide stapling has emerged as a versatile approach in drug discovery to reinforce secondary structure elements especially α-helices and improve properties of linear bioactive peptides. Inspired by the prevalence of arginine in protein-protein and protein-DNA interfaces, we investigated guanidinium-stapling as a means to constrain helical peptides. Guanidinium stapling was readily achieved on solid support, utilizing two orthogonally protected lysine or unatural α-amino acid residues with an amino function.

Anticoagulation, photoselective vaporization of the prostate and safety : a propensity score-matched study.

Purpose: We compared surgical complications after laser prostatic photovaporization in anticoagulated versus non-anticoagulated patients.

Methods: A propensity score was calculated and patients were matched, to compare postoperative complications using the Clavien-Dindo classification between the anticoagulated and non-anticoagulated groups. We also identified factors associated with complications, and perform an analysis of secondary endpoint with categories of urological complications.

Short Oligourea Foldamers as N- or C-Caps for Promoting α-Helix Formation in Water.

While foldamers have been extensively studied as protein mimics and especially as α-helix mimics, their use as capping motif to enhance α-helix propensity remains comparatively much limited. In this study, we leverage the structural similarities between urea-based helical foldamers and α-helix to investigate the efficacy of oligoureas as N- or C-caps for reinforcing α-helical structures in water. Short oligoureas, comprising 3 to 4 residues, were strategically introduced at the N- or C-terminus of two peptide sequences (S-peptide and an Ala-rich model sequence).