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ACS Central Science

Justin M Wolfe, Colin M Fadzen, Zi-Ning Choo, Rebecca L Holden, Monica Yao, Gunnar J Hanson, Bradley L Pentelute
Cell-penetrating peptides (CPPs) can facilitate the intracellular delivery of large therapeutically relevant molecules, including proteins and oligonucleotides. Although hundreds of CPP sequences are described in the literature, predicting efficacious sequences remains difficult. Here, we focus specifically on predicting CPPs for the delivery of phosphorodiamidate morpholino oligonucleotides (PMOs), a compelling type of antisense therapeutic that has recently been FDA approved for the treatment of Duchenne muscular dystrophy...
April 25, 2018: ACS Central Science
Dane Christie, Richard A Register, Rodney D Priestley
Nanoscale compositional heterogeneity in block copolymers can impart synergistic property combinations, such as stiffness and toughness. However, until now, there has been no experimental method to locally probe the dynamics at a specific location within these structured materials. Here, this was achieved by incorporating pyrene-bearing monomers at specific locations along the polymer chain, allowing the labeled monomers' local environment to be interrogated via fluorescence. In lamellar-forming poly(butyl methacrylate- b -methyl methacrylate) diblock copolymers, a strong gradient in glass transition temperature, T g , of the higher- T g block, 42 K over 4 nm, was mapped with nanometer resolution...
April 25, 2018: ACS Central Science
Abhishek Parija, Yun-Hyuk Choi, Zhuotong Liu, Justin L Andrews, Luis R De Jesus, Sirine C Fakra, Mohammed Al-Hashimi, James D Batteas, David Prendergast, Sarbajit Banerjee
Molybdenum disulfide (MoS2 ) is a semiconducting transition metal dichalcogenide that is known to be a catalyst for both the hydrogen evolution reaction (HER) as well as for hydro-desulfurization (HDS) of sulfur-rich hydrocarbon fuels. Specifically, the edges of MoS2 nanostructures are known to be far more catalytically active as compared to unmodified basal planes. However, in the absence of the precise details of the geometric and electronic structure of the active catalytic sites, a rational means of modulating edge reactivity remain to be developed...
April 25, 2018: ACS Central Science
Bong Geun Cha, Ji Hoon Jeong, Jaeyun Kim
Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the ex vivo culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes...
April 25, 2018: ACS Central Science
Atsushi Sakai, Yoshihiro Murayama, Kei Fujiwara, Takahiro Fujisawa, Saori Sasaki, Satoru Kidoaki, Miho Yanagisawa
Even though microgels are used in a wide variety of applications, determining their mechanical properties has been elusive because of the difficulties in analysis. In this study, we investigated the surface elasticity of a spherical microgel of gelatin prepared inside a lipid droplet by using micropipet aspiration. We found that gelation inside a microdroplet covered with lipid membranes increased Young's modulus E toward a plateau value E * along with a decrease in gel size. In the case of 5.0 wt % gelatin gelled inside a microsized lipid space, the E * for small microgels with R ≤ 50 μm was 10-fold higher (35-39 kPa) than that for the bulk gel (∼3 kPa)...
April 25, 2018: ACS Central Science
Emma E Watson, Xuyu Liu, Robert E Thompson, Jorge Ripoll-Rozada, Mike Wu, Imala Alwis, Alessandro Gori, Choy-Theng Loh, Benjamin L Parker, Gottfried Otting, Shaun Jackson, Pedro José Barbosa Pereira, Richard J Payne
The anophelins are small protein thrombin inhibitors that are produced in the salivary glands of the Anopheles mosquito to fulfill a vital role in blood feeding. A bioinformatic analysis of anophelin sequences revealed the presence of conserved tyrosine residues in an acidic environment that were predicted to be post-translationally sulfated in vivo . To test this prediction, insect cell expression of two anophelin proteins, from Anopheles albimanus and Anopheles gambiae , was performed, followed by analysis by mass spectrometry, which showed heterogeneous sulfation at the predicted sites...
April 25, 2018: ACS Central Science
Kenton J Hetrick, Mark C Walker, Wilfred A van der Donk
Peptide display has enabled identification and optimization of ligands to many targets. These ligands are usually linear or disulfide-containing peptides that are vulnerable to proteolysis or reduction. We report yeast surface and phage display of lanthipeptides, macrocyclic ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain multiple thioether cross-links that bestow their biological activities. We developed C-terminal yeast display of the class II lanthipeptides lacticin 481 and haloduracin β, and randomization of the C-ring of the former was used to select tight binders to αvβ3 integrin...
April 25, 2018: ACS Central Science
Liuqing Wen, Ding Liu, Yuan Zheng, Kenneth Huang, Xuefeng Cao, Jing Song, Peng George Wang
Abnormal expression of sialylated Thomsen-Friedenreich antigen (Neu5Acα2-3Galβ1-3GalNAcα-O-Ser/Thr, sialyl-T) has a strong relationship with various types of human cancers and many other diseases. However, the size and structural complexity, and relatively lower abundance of sialyl-T have posed a significant challenge to its detection. Therefore, details about the role of sialyl-T in a variety of physiological and pathological processes are still poorly understood. Here, a one-step chemoenzymatic labeling strategy to probe sialyl-T is described...
April 25, 2018: ACS Central Science
Shuai Yuan, Jun-Sheng Qin, Christina T Lollar, Hong-Cai Zhou
Group 4 metal-based metal-organic frameworks (MIV -MOFs), including Ti-, Zr-, and Hf-based MOFs, are one of the most attractive classes of MOF materials owing to their superior chemical stability and structural tunability. Despite being a relatively new field, MIV -MOFs have attracted significant research attention in the past few years, leading to exciting advances in syntheses and applications. In this outlook, we start with a brief overview of the history and current status of MIV -MOFs, emphasizing the challenges encountered in their syntheses...
April 25, 2018: ACS Central Science
Marcus I Gibson, Mohammad R Seyedsayamdost
No abstract text is available yet for this article.
April 25, 2018: ACS Central Science
Kyoung-Ku Kang, Chang-Soo Lee
No abstract text is available yet for this article.
April 25, 2018: ACS Central Science
Timothy P Lodge
No abstract text is available yet for this article.
April 25, 2018: ACS Central Science
Xing Chen
No abstract text is available yet for this article.
April 25, 2018: ACS Central Science
Sam Lemonick
No abstract text is available yet for this article.
April 25, 2018: ACS Central Science
Prachi Patel
No abstract text is available yet for this article.
April 25, 2018: ACS Central Science
Wenlin Zhang, Scott T Milner, Enrique D Gomez
Nematic order, in the bulk or at interfaces, is ubiquitous for semiflexible conjugated polymers. Nevertheless, the effect of liquid crystalline order on charge transport remains unclear. Using an analytical model, we demonstrate that nematic order leads to an enhancement in charge mobilities when compared to isotropic chains. Furthermore, we predict a quadratic dependence of the charge mobility on molecular weight of the chains. Analysis of the probability of forming hairpin defects also shows how the persistence length affects charge transport in conjugated polymers...
March 28, 2018: ACS Central Science
Theodore J Zwang, Edmund C M Tse, Dongping Zhong, Jacqueline K Barton
How birds sense the variations in Earth's magnetic field for navigation is poorly understood, although cryptochromes, proteins homologous to photolyases, have been proposed to participate in this magnetic sensing. Here, in electrochemical studies with an applied magnetic field, we monitor the repair of cyclobutane pyrimidine dimer lesions in duplex DNA by photolyase, mutants of photolyase, and a modified cryptochrome. We find that the yield of dimer repair is dependent on the strength and angle of the applied magnetic field even when using magnetic fields weaker than 1 gauss...
March 28, 2018: ACS Central Science
Alon Chapovetsky, Matthew Welborn, John M Luna, Ralf Haiges, Thomas F Miller, Smaranda C Marinescu
The bioinspired incorporation of pendant proton donors into transition metal catalysts is a promising strategy for converting environmentally deleterious CO2 to higher energy products. However, the mechanism of proton transfer in these systems is poorly understood. Herein, we present a series of cobalt complexes with varying pendant secondary and tertiary amines in the ligand framework with the aim of disentangling the roles of the first and second coordination spheres in CO2 reduction catalysis. Electrochemical and kinetic studies indicate that the rate of catalysis shows a first-order dependence on acid, CO2 , and the number of pendant secondary amines, respectively...
March 28, 2018: ACS Central Science
Ron Shah, Mikhail S Shchepinov, Derek A Pratt
Lipoxygenases (LOXs) have been implicated as central players in ferroptosis, a recently characterized cell death modality associated with the accumulation of lipid hydroperoxides: the products of LOX catalysis. To provide insight on their role, human embryonic kidney cells were transfected to overexpress each of the human isoforms associated with disease, 5-LOX, p12-LOX, and 15-LOX-1, which yielded stable cell lines that were demonstrably sensitized to ferroptosis. Interestingly, the cells could be rescued by less than half of a diverse collection of known LOX inhibitors...
March 28, 2018: ACS Central Science
Kurinji Krishnamoorthy, Kyle Hoffmann, Sumit Kewalramani, Jeffrey D Brodin, Liane M Moreau, Chad A Mirkin, Monica Olvera de la Cruz, Michael J Bedzyk
Protein-spherical nucleic acid conjugates (Pro-SNAs) are an emerging class of bioconjugates that have properties defined by their protein cores and dense shell of oligonucleotides. They have been used as building blocks in DNA-driven crystal engineering strategies and show promise as agents that can cross cell membranes and affect both protein and DNA-mediated processes inside cells. However, ionic environments surrounding proteins can influence their activity and conformational stability, and functionalizing proteins with DNA substantively changes the surrounding ionic environment in a nonuniform manner...
March 28, 2018: ACS Central Science
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