Peptides as invaluable tools in the search for innovative analgesics

Pain is a quite frequent complaint after injuries and accompanying different pathologies, which remains poorly treated for a number of patients. Pain involves extremely complex/interrelated series of signaling and modulatory pathways of the nervous system. Within them, the contribution to pain sensation and transmission of different ion channels and regulatory proteins center the attention in recent years. Here, peptides are paying a key role in better understanding how the direct modulation of these channels or the Continue reading

Thiol additive-free native chemical ligation

Native chemical ligation (NCL) commonly facilitates a peptide thioester with an N-terminal β-thiol peptide to form a native amide bond. Though many peptide thioester preparation strategies have been developed, it generally requires a large excess of exogenous thiol additives. Here I will discuss two recent reports focusing on thiol additive-free mediated NCL. For more please download PDF file. Contributed by Wenyi Li Wenyi Li received his doctoral degree by September 2016 in University of Melbourne Continue reading

Epigallocatechin Gallate – Unravelling its Effect on Amyloid and Toxic Oligomers

Many medical disorders are associated with amyloid formation, Alzheimer disease (AD) and Parkinson disease (PD) being perhaps the most well-known. All such diseases have in common the pathological aggregation of a normally soluble polypeptide chain into a series of oligomeric intermediates and ultimately into insoluble amyloid fibrils that accumulate within specific organs and tissues. The polyphenol (−)-epigallocatechin gallate (EGCG), extracted from green tea, is amongst the most promising small molecules with therapeutic potential to interfere Continue reading

Figuring Out the Configuration

Peptides can sometimes exhibit unusual stereochemistry.  Occasionally, for example, the usual l-amino acid building block might be substituted with its mirror-image counterpart. Such features can impact on function, but may be subtle enough to evade detection via routine methods. In this article, I highlight some innovative mass-spectrometry-based approaches to the characterisation of peptides with exotic stereochemical features. For more please download PDF file. Contributed by George Preston George is a Research Associate at King’s College Continue reading

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