Thanatin – an Insect-derived Antimicrobial Peptide Active against Pathogenic Gram-negative Bacteria

Swiss researchers have recently revealed the mechanism by which the insect-derived antimicrobial peptide thanatin targets the intermembrane protein complex required for lipopolysaccharide (LPS) transport in Escherichia coli. Employing a series of elegant techniques directed at increasing levels of magnification and ultimately, structural determination by NMR, these researchers show how thanatin interferes with assembly of the seven-member macromolecular protein complex which forms a molecular bridge supporting ATP-driven transport of LPS from the inner membrane to the Continue reading

Peptide vaccines: the future of immunotherapy?

It is widely accepted that vaccines are valuable preparations for prevention against life-threatening diseases such as polio, measles and smallpox and their utilization led to control and/or eradication of aforementioned infectious diseases. Common drawbacks in classical vaccine formulations led to the development of less allergenic and more specific peptide vaccines that usually consist of 20-30 amino acids and an external adjuvant to enhance immunogenicity of peptide epitopes, which are normally weak antigens and could therefore Continue reading

Targeted protein degradation as a new paradigm in drug discovery. Is there a role for peptides?

Despite the large number of new, therapeutically relevant proteins discovered in recent years, classical drug discovery strategies have not been particularly successful in finding suitable small-molecule modulators. Targeted protein degradation has raised considerable interest from pharmaceutical/biotech companies and academic groups as a novel paradigm in drug discovery. Two main strategies to generate protein degraders have been identified: 1) Protein-targeting chimeric molecules (PROTACs), and 2) Hydrophobic tagging (HyT). In the first case, multifunctional hybrid molecules containing Continue reading

Small Proteins, Big Data

The possibility that a subset of biological molecules has been overlooked, and is waiting to be discovered, is always intriguing. For small proteins (proteins of around 100 amino acid residues or fewer) there is evidence to suggest that this is indeed the case. In this article, I examine the defining characteristics of small proteins and survey the methods by which such proteins are analysed. The graphical abstract depicts NMR models of human sarcolipin (image of Continue reading

Inhibition of Amyloidogenesis by Synthetic Enantiomeric Peptides

A synthetic peptide composed of alternating L- and D-amino acid residues has been recently shown to inhibit aggregation and reduce toxic effects in neuroblastoma cells, of the beta-amyloid peptide, Aβ, implicated in Alzheimer’s disease. In contrast, a “twin” peptide with the same sequence, but with all L-amino acid residues, had no inhibitory effect on amyloidogenesis or toxicity of Aβ. For more please download PDF file. Contributed by Susan J. Tzotzos Susan Tzotzos works for the Continue reading

New enzymatic approaches for the generation of peptide and protein conjugates

Enzymatic conjugation of peptides and their analogues to other peptides or proteins is considered to be an exciting field in protein chemistry. Besides Sortase A, Butelase and Transglutaminase, the field offers attractive possibilities with respect to its broad spectrum and simplicity. Nevertheless, certain issues such as the length of the peptide tag, sophisticated purification protocols to separate enzymes from the product and high amounts of enzymes used limit the scope of these approaches. In this Continue reading

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