MALDI-imaging enables direct observation of kinetic and thermodynamic products of mixed peptide fiber assembly.

Controlling the self-assembly of multicomponent systems provides a key to designing new materials and understanding the molecular complexity of biology. Here, we demonstrate the first use of MALDI-imaging to characterize a multicomponent self-assembling peptide fiber. Observations of mixed peptide systems over time demonstrate how simple sequence variation can change the balance between kinetic and thermodynamic products.

Controlling gelation with sequence: Towards programmable peptide hydrogels.

Unlabelled: The self-assembling peptide IKHLSVN, inspired by inspection of a protein-protein interface, has previously been reported as one of a new class of bio-inspired peptides. Here the peptide, dubbed littleSven, and modifications designed to probe the resilience of the sequence to self-assembly, is characterised. Although the parent peptide did not form a hydrogel, small modifications to the sequence (one side chain or an N-terminus modification) led to hydrogels with properties (eg.

Synthesis and activity of a diselenide bond mimetic of the antimicrobial protein caenopore-5.

Antimicrobial proteins are a rich source of new lead compounds for the development of new drugs that will tackle global resistance towards existing antibiotics. Caenopore-5 () is an antimicrobial protein (AMP) expressed in the intestine of the nematode and is a member of the lipid binding saposin-like-protein family, composed of 5 α-helices and 3 disulfide bonds. Substitution of the Cys and Cys by two selenocysteine U and U afforded a selenocysteine analogue , which displayed a higher stability (using thermal circular dichroism) compared to the native protein .

The Nedd4-1 WW Domain Recognizes the PY Motif Peptide through Coupled Folding and Binding Equilibria.

The four WW domains of human Nedd4-1 (neuronal precursor cell expressed developmentally downregulated gene 4-1) interact with the PPxY (PY) motifs of the human epithelial Na(+) channel (hENaC) subunits, with the third WW domain (WW3*) showing the highest affinity. We have shown previously that the α-hENaC PY motif binding interface of WW3* undergoes conformational exchange on the millisecond time scale, indicating that conformational sampling plays a role in peptide recognition. To further understand this role, the structure and dynamics of hNedd4-1 WW3* were investigated.

Chemical synthesis of a pore-forming antimicrobial protein, caenopore-5, by using native chemical ligation at a glu-cys site.

The 2014 report from the World Health Organization (WHO) on antimicrobial resistance revealed an alarming rise in antibiotic resistance all around the world. Unlike classical antibiotics, with the exception of a few species, no acquired resistance towards antimicrobial peptides (AMPs) has been reported. Therefore, AMPs represent leads for the development of novel antibiotics.

Structure and dynamics of human Nedd4-1 WW3 in complex with the αENaC PY motif.

Nedd4-1 (neuronal precursor cell expressed developmentally downregulated gene 4-1) is an E3 ubiquitin ligase that interacts with and negatively regulates the epithelial Na(+) channel (ENaC). The WW domains of Nedd4-1 bind to the ENaC subunits via recognition of PY motifs. Human Nedd4-1 (hNedd4-1) contains four WW domains with the third domain (WW3*) showing the strongest affinity to the PY motif.