Bioorthogonal labeling of peptides and proteins-two recent examples

Site-specific introduction of distinct molecules into proteins and peptides is a challenging task. It becomes even more challenging if the labeling reaction has to be performed in living systems. How can we overcome undesired cross reactions with functional groups on proteins other than our target and decrease the immunogenicity of the external starting materials? Bioorthogonal chemistry provides a solution for this kind of questions. In this commentary, I will focus on two new methods, irreversible Continue reading

Where is the field of α-helix mimetics going?

Protein-protein interactions (PPI) are promiscuous in many biological pathways and their dysfunction is related to several pathologies. Therefore, PPI modulators are not only important probes to understand biological processes, but potential agents for pharmaceutical intervention. Taking into account the high incidence of α–helices within therapeutically relevant PPI interfaces, the big efforts devoted to develop α–helix mimetics is not surprising. In recent years, these effort have been mainly related, on one hand, to the development of Continue reading

Pre-clinical Study Confirms Potential of Peptide Hydrogels As Localised Drug Delivery Vehicles

Hydrogel-forming peptides have the ability to self-assemble into nanofibres, which can further form 3D networks of entangled fibrous structures, essentially affording a scaffold-like architecture. Within minutes of adding these short peptides to water in appropriate proportions, a gel is formed, hence the characteristic name. A recent pre-clinical study using radiolabelled peptide monomers has confirmed the potential application of peptide hydrogels as drug delivery vehicles. Contributed by Susan J. Tzotzos For more please download PDF file.

Non-Canonical Building Blocks Extend the Peptide Alphabet

The use of non-canonical amino-acid building blocks for peptide synthesis is a flexible way of introducing functionalities not normally found in biological systems. Two recent papers on this theme, both from Journal of Peptide Science, are discussed. In the first (Grob et al., 2017), methionine analogues are used to suppress side reactions in the synthesis of a radiopharmaceutical; in the second (Pícha et al., 2017) practical considerations for syntheses of azide-containing building blocks are explored. Continue reading

Native Chemical Ligation and Beyond: Recent Developments in Chemical Protein Synthesis

The total chemical synthesis of proteins has been one of the most challenging topics of organic chemistry in 20th century. The discovery of solid phase peptide synthesis (SPPS) in 1963 by R.B. Merrifield and the development of native chemical ligation (NCL) in 1994 by Kent and coworkers enabled the synthesis of large proteins. Moreover, NCL expanded the scope of total chemical protein synthesis immensely by allowing site-specific introduction of native and artificial modifications. Researchers continuously Continue reading

Will the discovery of cross-α amyloid-like fibrils herald a new definition of amyloid?

In microorganisms, functional amyloid is often involved in virulence mechanisms. Staphylococcus aureus secretes a 22-residue phenol-soluble modulin α3 (PSMα3) peptide, capable of forming elongated fibrils, with the appearance and staining properties typical of amyloid. Researchers working to solve the 3D structure of PSMα3 fibrils by X-ray crystallography were in for a surprise. As reported by Tayeb-Fligelman et al in their recent publication in Science, fibrils of PSMα3 revealed a distinctive “cross-α” amyloid-like architecture instead of Continue reading

Antimicrobial Peptides: Alternatives To Combat Bacterial Infections

Due to the increasingly growth of antibiotics resistance, antimicrobial peptides (AMPs) with multiple modes of action have been considered as the alternatives to combat pathogens. Here, we discussed two recent research publications about the development of AMPs. The first example published on J. Pept. Sci. demonstrated the N-terminal modification with lipid acid significantly improved the cationic AMPs’ antibacterial and antifungal activities with secondary structure changes. The other research article combined in silico computational screening tool Continue reading

Cyclic Peptides in Biological/Medicinal Chemistry

In biological and medicinal chemistry, cyclic peptides have advantages over linear analogues, because of their enhanced metabolic stability and a better definition of their conformational mobility. In recent years, there has been a considerable increase in the use of cyclic peptides as tools to better understand relevant biological processes and to search for new therapeutic agents. This was especially important for the study and development of new molecular entities to modulate protein-protein interactions, in which Continue reading

Cysteine: an Essential Inessential Amino Acid

Cysteine is not, of course, one of the ten “essential” proteinogenic α-amino acids that mammals require in their diet. In many other respects, however, cysteine is just as important as any of the “essential” amino acids (or, for that matter, any of the other nine “inessential” ones). In fact, one could go as far as to call cysteine a special amino acid because of the rich chemistry of its thiol group. It is from this Continue reading

Daptomycin – A New Twist To An Old Tale

Daptomycin is no newcomer to the stage of antibiotics, yet its mechanism of action has been a source of controversy since its discovery over 30 years ago. Exciting results of a collaborative study between scientists in The Netherlands, Germany and the UK reported recently in PNAS (24th October), have cleared this controversy, shedding new light onto how daptamycin kills bacteria and providing a fresh perspective of the model of the cell membrane applied to antimicrobial Continue reading