Aromatic Foldamer Helices as α-Helix Extended Surface Mimetics.

Helically folded aromatic oligoamide foldamers have a size and geometrical parameters very distinct from those of α-helices and are not obvious candidates for α-helix mimicry. Nevertheless, they offer multiple sites for attaching side chains. It was found that some arrays of side chains at the surface of an aromatic helix make it possible to mimic extended α-helical surfaces.

Selenolysine: A New Tool for Traceless Isopeptide Bond Formation.

Despite their biological importance, post-translationally modified proteins are notoriously difficult to produce in a homogeneous fashion by using conventional expression systems. Chemical protein synthesis or semisynthesis offers a solution to this problem; however, traditional strategies often rely on sulfur-based chemistry that is incompatible with the presence of any cysteine residues in the target protein. To overcome these limitations, we present the design and synthesis of γ-selenolysine, a selenol-containing form of the commonly modified proteinogenic amino acid, lysine.

Structure Elucidation of Helical Aromatic Foldamer-Protein Complexes with Large Contact Surface Areas.

The development of large synthetic ligands could be useful to target the sizeable surface areas involved in protein-protein interactions. Herein, we present long helical aromatic oligoamide foldamers bearing proteinogenic side chains that cover up to 450 Å of the human carbonic anhydrase II (HCA) surface. The foldamers are composed of aminoquinolinecarboxylic acids bearing proteinogenic side chains and of more flexible aminomethyl-pyridinecarboxylic acids that enhance helix handedness dynamics.

Small molecule diselenide additives for in vitro oxidative protein folding.

The in vitro oxidative folding of disulfide-rich proteins can be challenging. Here we show a new class of small molecule diselenides, which can be easily prepared from inexpensive starting materials, used to enhance oxidative protein folding. These compounds were tested on a model protein, bovine pancreatic trypsin inhibitor.

Chemical Synthesis of Proteins with Non-Strategically Placed Cysteines Using Selenazolidine and Selective Deselenization.

Although native chemical ligation has enabled the synthesis of hundreds of proteins, not all proteins are accessible through typical ligation conditions. The challenging protein, 125-residue human phosphohistidine phosphatase 1 (PHPT1), has three cysteines near the C-terminus, which are not strategically placed for ligation. Herein, we report the first sequential native chemical ligation/deselenization reaction.

Insights into the deselenization of selenocysteine into alanine and serine.

The development of native chemical ligation coupled with desulfurization has allowed ligation at several new ligation junctions. However, desulfurization also converts all cysteine residues in the protein sequence into alanine. Deselenization of selenocysteine, in contrast, selectively removes the selenol group to give alanine in the presence of unprotected cysteines.

Synthesis of new β(2,2)-amino acids with carbohydrate side chains: impact on the synthesis of peptides.

The study describes the synthesis of new geminally disubstituted C-linked carbo-β(2,2)-amino acids (β(2,2)-Caas) with different carbohydrate side chains, and their use in the synthesis of β(2,2)-peptides. The study infers that the side chain has an influence on the synthesis of peptides and their conformational behaviour.

Synthesis and structural studies of homooligomers of geminally disubstituted β(2,2)-amino acids with carbohydrate side chain.

A new class of geminally disubstituted C-linked carbo-β(2,2)-amino acids (β(2,2)-Caa) were prepared from d-glucose. The structures of homooligomeric di-, tetra-, and hexapeptides prepared from (S)-β(2,2)-Caa were studied with NMR (in CDCl(3)), CD, and Molecular Dynamics calculations. These β(2,2)-peptides have shown the presence of stable 6-membered (6-mr) NH(i)···CO(i) intra-residue H-bonded (C(6)) strands.