Grafted Coiled-Coil Peptides as Multivalent Scaffolds for Protein Recognition.

Self-assembled peptides are promising templates for the design of inhibitors of protein-protein interactions (PPIs) because they can be endowed with affinity- and selectivity-defining amino acids alongside favorable physicochemical properties such as solubility and stability. Here, we describe a tunable coiled-coil scaffold and its interaction with MCL-1, an α-helix-binding antiapoptotic protein and important target in oncology. We explore the role of oligomerization, multivalency, and cooperativity in PPI inhibition.

Correction to "Scalable Inhibitors of the Nsp3-Nsp4 Coupling in SARS-CoV-2".

[This corrects the article DOI: 10.1021/acsomega.2c06384.

Scalable Inhibitors of the Nsp3-Nsp4 Coupling in SARS-CoV-2.

The human Betacoronavirus SARS-CoV-2 is a novel pathogen claiming millions of lives and causing a global pandemic that has disrupted international healthcare systems, economies, and communities. The virus is fast mutating and presenting more infectious but less lethal versions. Currently, some small-molecule therapeutics have received FDA emergency use authorization for the treatment of COVID-19, including Lagevrio (molnupiravir) and Paxlovid (nirmaltrevir/ritonavir), which target the RNA-dependent RNA polymerase and the 3CLpro main protease, respectively.

How to Design Peptides.

Novel design of proteins to target receptors for treatment or tissue augmentation has come to the fore owing to advancements in computing power, modeling frameworks, and translational successes. Shorter proteins, or peptides, can offer combinatorial synergies with dendrimer, polymer, or other peptide carriers for enhanced local signaling, which larger proteins may sterically hinder. Here, we present a generalized method for designing a novel peptide.

Angiogenic Hydrogels to Accelerate Early Wound Healing.

Diabetes mellitus affects an increasing proportion of the population, and is projected to double by 2060. Comorbidities contribute to an interrupted healing process which is delayed, prolonged, and associated with increased susceptibility to infection and unresolved inflammation. This leads to chronic nonhealing wounds and potential amputation.

Peptide-Based Inhibitors for SARS-CoV-2 and SARS-CoV.

The COVID-19 (coronavirus disease) global pandemic, caused by the spread of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited treatment options which include vaccines, anti-virals, and repurposed therapeutics. With their high specificity, tunability, and biocompatibility, small molecules like peptides are positioned to act as key players in combating SARS-CoV-2, and can be readily modified to match viral mutation rate. A recent expansion of the understanding of the viral structure and entry mechanisms has led to the proliferation of therapeutic viral entry inhibitors.

Control of Collagen Triple Helix Stability by Phosphorylation.

The phosphorylation of the collagen triple helix plays an important role in collagen synthesis, assembly, signaling, and immune response, although no reports detailing the effect this modification has on the structure and stability of the triple helix exist. Here we investigate the changes in stability and structure resulting from the phosphorylation of collagen. Additionally, the formation of pairwise interactions between phosphorylated residues and lysine is examined.

Glycine Substitutions in Collagen Heterotrimers Alter Triple Helical Assembly.

Osteogenesis imperfecta typically results from missense mutations in the collagen genome where the required glycine residues are replaced with another amino acid. Many models have attempted to replicate the structure of mutated collagen on the triple helix level. However, composition and register control of the triple helix is complicated and requires extreme precision, especially when these destabilizing mutations are present.

Treatment of hind limb ischemia using angiogenic peptide nanofibers.

For a proangiogenic therapy to be successful, it must promote the development of mature vasculature for rapid reperfusion of ischemic tissue. Whole growth factor, stem cell, and gene therapies have yet to achieve the clinical success needed to become FDA-approved revascularization therapies. Herein, we characterize a biodegradable peptide-based scaffold engineered to mimic VEGF and self-assemble into a nanofibrous, thixotropic hydrogel, SLanc.

Synthetic, Register-Specific, AAB Heterotrimers to Investigate Single Point Glycine Mutations in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a disease caused primarily by mutations of glycine in the standard (Xaa-Yaa-Gly)n repeat of a type I collagen triple helix. Type I collagen is an AAB heterotrimer which means that, depending on whether the A or B chain is mutated, the glycine substitution will appear once or twice. In this work we use designed axial charged pairs to self-assemble an AAB triple helix with controlled composition and register.

Comparative NMR analysis of collagen triple helix organization from N- to C-termini.

The collagen triple helix consists of three supercoiled solvent-exposed polypeptide chains, and by dry weight it is the most abundant fold in mammalian tissues. Many factors affecting the structure and stability of collagen have been determined through the use of short synthetically prepared peptides, generally called collagen-mimetic peptides (CMPs). NMR (nuclear magnetic resonance spectroscopy) investigations into the molecular structure of CMPs have suffered from large amounts of signal overlap and degeneracy because of collagen's repetitive primary sequence, the close and symmetric packing of the three chains and the identical peptide sequences found in homotrimers.