Nanosphere lithography offers a rapid, low-cost approach for patterning of large-area two-dimensional periodic nanostructures. However, a complete understanding of the nanosphere self-assembly process is necessary to enable further development and scaling of this technology. The self-assembly of nanospheres into two-dimensional periodic arrays has previously been attributed solely to the Marangoni force; however, we demonstrate that the ζ potential of the nanosphere solution is critically important for successful self-assembly to occur. We discuss and demonstrate how this insight can be used to greatly increase self-assembled 2D periodic array areas while decreasing patterning time and cost. As a representative application, we fabricate antireflection nanostructures on a transparent flexible polymer substrate suitable for use as a large-area (270 cm2), broadband, omnidirectional antireflection film.The first total synthesis of the bicyclic depsipeptide natural product seongsanamide B is described. The successful approach employed solid-phase peptide synthesis of a core heptapeptide, incorporating on-resin esterification, followed by solution-phase macrolactamization and a late stage intramolecular Evans-Chan-Lam coupling to generate the biaryl ether of the isodityrosine unit.β-Turn tetrapeptides were demonstrated to catalyze asymmetric aldol reaction of α-branched aldehydes and α-carbonyl aldehydes, i.e. glyoxylates and α-ketoaldehydes, to biomimetically synthesize acyclic all-carbon quaternary center-bearing 1,4-dicarbonyls in high yield and excellent enantioselectivity under mild conditions. SC-43 The spatially restricted environment of the tetrapeptide warrants high enantioselectivity and yield with broad substrates. Using this protocol, (R)-pantolactone, the key intermediate of vitamin B5, was readily accessed in a practical, efficient, and environmentally benign process from inexpensive starting materials.The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.Recent experimental data has shown that protein folding in the cytoplasm can differ from in vitro folding with respect to speed, stability, and residual structure. Here we investigate the all-atom molecular dynamics (MD) simulations of 9 copies of the model protein GTT WW domain in a small bacterial cytoplasm model using three force fields. GTT has been well-studied by MD in aqueous solution for comparison. We find that folded copies remain folded for up 25 μs, whereas unfolded copies do not fold for up to 190 μs. Unfolded GTT in our cytoplasm model does populate partly folded intermediates with one of the two hairpins formed. Relative to aqueous solution, GTT gets stuck in metastable states with a small RMSD and radius of gyration and extensive burial of surface area against other macromolecules. In particular, GTT is even able to form transient intermolecular β-sheets with other proteins, resulting in a “chimeric structure” that could be a precursor to oligomeric β-aggregates. We conclude that sticking, enhanced by the non-native mutations of GTT, is largely responsible, and we propose, on the basis of our result as well as recent experiments, that coevolution of protein surfaces with their solvation environment (including chaperones) is important for folding and diffusion of proteins in the cytoplasm.Pathogenic thrombus formation accounts for the aetiology of many serious conditions including myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. Despite the development of numerous anticoagulants and antiplatelet agents, the mortality rate associated with these diseases remains high. In recent years, however, significant epidemiological evidence and clinical models have emerged to suggest that modulation of the GPVI platelet receptor could be harnessed as a novel antiplatelet strategy. As such, many peptidic agents have been described in the last decade, whilst more recent efforts have focused on the development of small molecule modulators. Herein the rationale for targeting GPVI is summarised and the published GPVI modulators are reviewed, with particular focus on small molecules. A qualitative pharmacophore hypothesis for small molecule ligands at GPVI is also presented.Human aldo-keto reductase family 1 member C3 (AKR1C3) is known as a hormone activity regulator and prostaglandin F (PGF) synthase that regulates the occupancy of hormone receptors and cell proliferation. Because of the overexpression in metabolic diseases and various hormone-dependent and -independent carcinomas, as well as the emergence of clinical drug resistance, an increasing number of studies have investigated AKR1C3 inhibitors. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We propose our viewpoints on the current problems associated with AKR1C3 inhibitors with the aim of providing a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.We have synthesized a number of Quillaja saponaria Molina (QS) saponin analogues with a different C28 sugar unit, which features either 3,4-diacetyl groups or a 3,4-cyclic carbonate group at the reducing end fucoside to mimic the naturally occurring saponin adjuvant QS-7. Immunological evaluations of these analogues in BALB/c mice indicate that truncating the C28 oligosaccharide of the natural product to the tetrasaccharide (as in 5d (β)) could retain the adjuvant’s activity in enhancing IgG1 and IgG2a productions, albeit the activity is lower than that of QS-21. Further truncation or changing stereochemistry of glycosidic linkage between the tetrasaccharide and the triterpenoid quillaic acid (QA) core or within the tetrasaccharide eliminated the saponins’ adjuvant activity in terms of IgG production. On the other hand, increasing resemblance to QS-7 increased adjuvant activity and led to saponin 3’s similar IgG1 and IgG2a activities to QS-21’s, indicating that the unique adjuvant activities of QS saponins are determined by their specific structures.