Development of Insulin-Like Growth Factor Mimetic Materials.

Growth factors play a crucial role in regulating cellular processes such as proliferation, differentiation, and survival. Their activities are tightly modulated to ensure proper physiological functioning, with dysregulation often contributing to disease pathogenesis. Among these, the insulin-like growth factor (IGF) system that encompasses IGF-1 and IGF-receptor binding proteins is pivotal in maintaining overall cellular health by regulating growth, repair, and metabolic regulation.

Neurobiological and Chemical Characterization of the Cyanobacterial Metabolite Veraguamide E.

Ver E's structure was validated by H NMR, HRMS, and molecular networking analyses. Computational docking and NMR titration confirmed direct, saturable, and tight binding of Ver E to the human Sigma-2 receptor/transmembrane protein 97 (σR/TMEM97). Functional calcium imaging in primary mouse sensory neurons revealed that Ver E increases intracellular Ca levels without modulating store-operated calcium entry (SOCE).

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

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

Structural Consequences of Introducing Bioactive Domains to Designer β-Sheet Peptide Self-Assemblies.

We applied solid- and solution-state nuclear magnetic resonance spectroscopy to examine the structure of multidomain peptides composed of self-assembling β-sheet domains linked to bioactive domains. Bioactive domains can be selected to stimulate specific biological responses (., receptor binding), while the β-sheets provide the desirable nanoscale properties.

Antiviral fibrils of self-assembled peptides with tunable compositions.

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized β-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions.

Injectable Peptide Hydrogels Loaded with Murine Embryonic Stem Cells Relieve Ischemia after Myocardial Infarction.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, especially in aging and metabolically unhealthy populations. A major target of regenerative tissue engineering is the restoration of viable cardiomyocytes to preserve cardiac function and circumvent the progression to heart failure post-MI. Amelioration of ischemia is a crucial component of such restorative strategies.

Rational Design of de novo CCL2 Binding Peptides.

Chronic levels of inflammation lead to autoimmune diseases such as rheumatoid arthritis and atherosclerosis. A key molecular mediator responsible for the progression of these diseases is Chemokine C-C motif ligand 2 (CCL2), a homodimerized cytokine that dissociates into monomeric form and binds to the CCR2 receptor. CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), attracts monocytes to migrate to areas of injury and mature into macrophages, leading to positive feedback inflammation with further release of proinflammatory molecules such as IL-1β and TNF-α.

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.

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.