Small peptide and amino acid derivatives in the search for SARS-CoV2 main protease inhibitors

In times of COVID-19 pandemic, science is advancing very fast, faster than ever. The first vaccines and various diagnosis probes are already in the market. There is an approved drug, remdesivir, and intensive work is being done on drug repurposing, with massive studies in clinical trials. In this highlight, I would like to call your attention on small peptides and amino acid derivatives able to inhibit SARS-CoV2 main protease (Mpro). Originated from previous knowledge on Continue reading

Peptide Therapeutics for COVID-19

As the world struggles to cope with the current COVID-19 pandemic, in this edition of “Peptide Highlights” we present a survey of peptide drugs which are being investigated as potential therapies for the disease. For more please download PDF file. Contributed by Susan J. Tzotzos Susan Tzotzos works for the Vienna-based biotech company Apeptico Forschung & Entwicklung GmbH, where she designs therapeutic peptides, oversees their synthesis and follows up their application in clinical trials. Susan Continue reading

Imine-derived macrocyclic peptides

In recent years, macrocyclic peptides are attracting a growing attention of pharmaceutical/biotech companies and academic groups. Their intermediate size, in-between small-molecule drugs and biotherapeutics, enable their utility as modulators of therapeutically relevant protein-protein interactions (PPIs), while they are still synthetically accessible facilitating medicinal chemistry programs. In this respect, macrocyclic peptides are important chemical tools on the road to PPI modulation to interrogate biological systems and to advance in the treatment of unmet medical needs. Within Continue reading

Life imitates cookery: lysinoalanine crosslinks in peptides and proteins

The lysinoalanine crosslink – a type of protein post-translational modification – was initially discovered in vitro and later found to occur in cooked and processed food. Curiously, the same kind of crosslink occurs in certain peptide antibiotics; and there is evidence to suggest that it also occurs in the flagella of some bacteria. This article highlights recent research on lysinoalanine crosslinks and their mechanisms of formation. For more please download PDF file. Contributed by George Continue reading

The hitchhiker´s guide to chemoselectivity in chemical protein synthesis

Posttranslational modifications (PTMs) allow proteins to perform a variety of physiological functions. Thus, it is of prime importance to elucidate their role on proteins in physiological and/or pathophysiological processes. However, molecular biological methods to generate proteins either does not yield in proteins with PTMs (E. coli) or give rise to heterogeneous mixture thereof (mammalian cells). To provide homogeneity, different chemoselective ligation methods such as native chemical ligation (NCL) were used successfully to associate peptide segments Continue reading

Peptide Drugs of the Decade

The approaching end of another decade prompted this short review of peptide drugs that successfully reached the European market from 2010 to the present. The article also gives a comparison of numbers of marketing authorisations granted to peptide drugs in Europe and the US over the last two decades as well as a glimpse of trends in the evolution of peptide drug development. For more please download PDF file. Contributed by Susan J. Tzotzos Susan Continue reading

“Sweet” Peptides

Naturally occurring glycopeptides (GPs, peptide + sugar) and glycoproteins are crucial players in many biological processes. N- and O-glycosylation is in fact one of the most important post-translational modifications in vivo. Glycoproteins are fundamental in cell-cell communications, recognition of viruses and bacteria by host cells, and tumor progression. Therefore, GPs can be used for emulating glycoprotein epitopes, and as such are recognized as important conjugates for immunostimulation and vaccines. In the drug discovery field, the attachment Continue reading

The Other Sanger Sequencing

Inspired by a recent celebration of the work of Martin and Synge, this article examines the role of chromatography in efforts to elucidate the primary structures of proteins. It touches on, as I have referred to it, ‘the other Sanger sequencing’ – the method by which the first protein sequence was determined. It goes on to highlight some recent work on the application of a displacement method to the separation of peptides (Kwiatkowski et al., Continue reading

Why protein chemist chose phosphorus for protein bioconjugation?

In the last two decades, phosphorus-mediated chemoselective ligation reactions acquired the “gold” status for in vivo labeling of biomolecules. However, some drawbacks of phosphines, such as directing non-canonical amino acids (e.g. azides) as their reaction partners limits the scope of these reactions. Thus, for chemical approaches, targeting canonical amino acids on proteins as targets for site-specific conjugation are of prime importance. Indeed, protein chemists developed several methods using canonical amino acids as selective conjugation sites. Continue reading

Conjugates of Vancomycin and Cell-penetrating Peptides – New Weapons in the Armoury against Drug Resistant Bacteria

Staying one step ahead in the arms race against antibiotic resistant pathogenic bacteria is an ongoing challenge to the ingenuity of medicinal chemists. Multidrug-resistance has become a menacing threat to the antibiotic armoury used by clinicians to treat nosocomial and community-acquired bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most notorious of such hospital-acquired pathogens. Until recently, the glycopeptide antibiotic vancomycin (Van) was available as a last resort, to effectively treat patients suffering Continue reading