Wim Schepens

The First One-Pot Synthesis of l-7-Iodotryptophan from 7-Iodoindole and Serine, and an Improved Synthesis of Other l-7-Halotryptophans

A simple and scalable one-pot biotransformation enables direct access to L-halotryptophans, including L-7-iodotryptophan, from the corresponding haloindoles. The biotransformation utilizes an easy to prepare bacterial cell lysate that may be stored as the lyophilizate for several months and utilized as a catalyst as and when required.

Potent peptidic fusion inhibitors of influenza virus

Broadly reactive drugs for flu Drugs for influenza are limited. For those available, viral resistance is rife. Part of the problem is that the virus is constantly mutating. Kadam et al. tested the cell entry stage of the virus life cycle as a drug target (see the Perspective by Whitehead). Cell entry is mediated by the major surface glycoprotein hemagglutinin (HA). This stage can be blocked by broadly neutralizing antibodies binding to HA. The authors generated small cyclic peptides that bind to the same sites on HA as the antibodies and mimic their activity. The peptides are cheap and easy to synthesize, are nontoxic to mice, and prevented infection of cells by many types of influenza virus. Science, this issue p. 496; see also p. 450 Peptide mimics of broadly neutralizing antibodies target the cell fusion stem region of the virus hemagglutinin and have potential as drugs. Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

Suzuki–Miyaura Diversification of Amino Acids and Dipeptides in Aqueous Media

The Suzuki–Miyaura derivatisation of free amino acids, peptides and proteins is an attractive area with considerable potential utility for medicinal chemistry and chemical biology. Here we report the modification of unprotected and Boc‐protected aromatic amino acids and dipeptides in aqueous media, enabling heteroarylation and vinylation. We systematically investigate the impact of the peptide backbone and adjacent amino acid residues upon the reaction. Our studies reveal that although asparagine and histidine hinder the reaction, by utilising dppf, a ferrocene‐based bidentate phosphine ligand, cross coupling of halophenylalanine or halotryptophan adjacent to such a residue could be enabled. Our studies reveal dppf to have good compatibility with all unprotected, proteinogenic amino acid side chains.