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Peptide mimics

Bing Cao, Fengfeng Xiao, Da Xing, Xianglong Hu
The increased threat of antibiotic resistance has created an urgent need for new strategies. Herein, polyprodrug antimicrobials are proposed to mimic antimicrobial peptides appended with a concurrent drug release property, exhibiting broad-spectrum antibacterial activity and especially high potency to inhibit methicillin-resistant Staphylococcus aureus (MRSA) without inducing resistance. Two series of polyprodrug antimicrobials are fabricated by facile polymerization of triclosan prodrug monomer (TMA) and subsequent quaternization of hydrophilic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), affording PDMAEMA-b-PTMA and PQDMA-b-PTMA, respectively...
August 17, 2018: Small
Caixing Xiong, Krzysztof Kaczmarek, Janusz Zabrocki, Patricia V Pietrantonio, Ronald J Nachman
Insect kinins modulate aspects of diuresis, digestion, development, and sugar taste perception in tarsi and labellar sensilla in mosquitoes. They are, however, subject to rapid biological degradation by endogenous invertebrate peptidases. A series of α-aminoisobutyric (Aib) acid-containing insect kinin analogs incorporating sequences native to the Aedes aegypti mosquito aedeskinins were evaluated on two recombinant kinin invertebrate receptors stably expressed in cell lines, discovering a number of highly potent and biostable insect kinin mimics...
August 11, 2018: General and Comparative Endocrinology
Benjamin Des Soye, Samuel Davidson, Matthew Weinstock, Dan Gibson, Michael C Jewett
A new wave of interest in cell-free protein synthesis (CFPS) systems has shown their utility for producing proteins at high titers, establishing genetic regulatory element libraries (e.g., promoters, ribosome binding sites) in non-model organisms, optimizing biosynthetic pathways before implementation in cells, and sensing biomarkers for diagnostic applications. Unfortunately, most previous efforts have focused on a select few model systems, such as Escherichia coli. Broadening the spectrum of organisms used for CFPS promises to better mimic host cell processes in prototyping applications and open up new areas of research...
August 14, 2018: ACS Synthetic Biology
Bo Wang, Joseph W LaMattina, Edward D Badding, Lauren K Gadsby, Tyler L Grove, Squire J Booker
Thiopeptide natural products have gained interest recently for their diverse pharmacological properties, including antibacterial, antifungal, anticancer, and antimalarial activities. Due to their inherent poor solubility and uptake, there is interest in developing new thiopeptides that mimic these unique structures, but which exhibit better pharmacokinetic properties. One strategy is to exploit the biosynthetic pathways using a chemoenzymatic approach to make analogs. However, a complete understanding of thiopeptide biosynthesis is not available, especially for those molecules that contain a large number of modifications to the thiopeptide core...
2018: Methods in Enzymology
Xiujuan Zhang, Xiaohui Ding, Yuanmei Zhu, Huihui Chong, Sheng Cui, Jinsheng He, Xinquan Wang, Yuxian He
OBJECTIVE: The peptide drug T20 (enfuvirtide), derived from the C-terminal heptad repeat region of HIV-1 gp41, is the only membrane fusion inhibitor available for treatment of viral infection; however, its mechanism of action remains elusive and its structural basis is lacking. DESIGN: We focused on determining the crystal structure of T20 in complex with N39, a target mimic peptide derived from the N-terminal heptad repeat region of gp41. Based on the structural information, the mechanisms of action of T20 and its resistance were further characterized...
August 8, 2018: AIDS
Tiehui Wang, Yehfang Hu, Eakapol Wangkahart, Fuguo Liu, Alex Wang, Eman Zahran, Kevin R Maisey, Min Liu, Qiaoqing Xu, Mónica Imarai, Christopher J Secombes
Mammalian interleukin (IL)-2 is a cytokine centrally involved in the differentiation and survival of CD4+ T helper subsets and CD4+ T regulatory cells and in activation of cytotoxic effector lymphocytes. In bony fish, IL2 orthologs have been identified with an additional divergent IL2-Like gene on the same locus present in several fish species. We report here two divergent IL2 paralogs, IL2A and IL2B , in salmonids that originated from the whole genome duplication event in this fish lineage. The salmonid IL2 paralogs differ not only in sequence but also in exon sizes...
2018: Frontiers in Immunology
Stanley Dumeus, Marthandam Asokan Shibu, Wan-Teng Lin, Ming-Fu Wang, Chao-Hung Lai, Chia-Yao Shen, Yueh-Min Lin, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
BACKGROUND/AIMS: High-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) poses therapeutic challenges in elderly subjects. Due to lack of efficient drug therapy, plant-based bioactive peptides have been studied as alternative strategy in NAFLD and for less toxicity in elderly. To mimic fatty liver in aging conditions, researchers highly commended the genetically engineered strains SAMP8 (senescence-accelerated mice prone 8). However, there is a paucity of reports about the anti-steatosis effects of bioactive peptides against fatty liver development under a combined action of high-fat diet exposure and aging process...
August 9, 2018: Cellular Physiology and Biochemistry
Fulvio Perrella, Umberto Raucci, Maria Gabriella Chiariello, Marco Chino, Ornella Maglio, Angela Lombardi, Nadia Rega
Fe(III)-Mimochrome VI (MC6) is a recently reported artificial heme-peptide conjugate system with a high peroxidase-like activity. By design, its structure features a five-coordinated Fe(III)-deuteroporphyrin active site, embedded in a compact α-helix-heme-α-helix "sandwich" motif. Up to now, no detailed MC6 structural characterization is available. In this work we propose a theoretical investigation based on molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular mechanics (QM/MM) optimizations, aimed to shed light on several Fe(III)-MC6 structural features and to validate the de novo designed fold...
August 9, 2018: Biopolymers
Jie Ren, Wei Liu, Guang-Cai Li, Meng Jin, Zhen-Xi You, Hui-Guo Liu, Yi Hu
Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH). However, little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy, and whether specific hypertrophyrelated microRNAs are involved in the modulation. MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia. This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy...
June 2018: Current medical science
Lifei Yang, Shailendra Kumar Sharma, Christopher Cottrell, Javier Guenaga, Karen Tran, Richard Wilson, Anna-Janina Behrens, Max Crispin, Natalia de Val, Richard T Wyatt
Soluble HIV-1 envelope glycoprotein (Env) trimers are under active investigation as vaccine candidates in relevant pre-clinical models. Like SOSIPs, the cleavage-independent native flexibly linked (NFL) trimers are faithful mimics of the Env spike. Here, we analyzed multiple new designs to explore alternative modifications, informing tertiary interactions, while maintaining NFL trimer homogeneity and integrity. Accordingly, we performed a proline (P) substitution screen in the gp41 heptad repeat 1 region, identifying other trimer-enhancing Ps, including L555P...
2018: Frontiers in Immunology
Yang Xu, Hongwei Yang, Zhibing Huang, Yanping Li, Qinghua He, Zhui Tu, Yanwei Ji, Wenjie Ren
A deoxynivalenol (DON) epitope clone (D8 ) was obtained by phage display technology using anti-DON monoclonal antibodies as a target molecule. Subsequently, a DON antigen mimic (D8 -maltose-binding protein [MBP]) was synthesized by fusing the mimic epitope peptide with MBP. An enzyme-linked immunosorbent assay (ELISA) and urchin-like gold nanoparticle immunochromatographic assay was developed based on D8 -MBP for detection of DON in maize and wheat. The half-maximal inhibitory concentration, lower detection limit, and linear range of the D8 -MBP ELISA were 57...
December 1, 2018: Food Chemistry
Albert van Dijk, Chris J Hedegaard, Henk P Haagsman, Peter M H Heegaard
Innate defense mechanisms are aimed at quickly containing and removing infectious microorganisms and involve local stromal and immune cell activation, neutrophil recruitment and activation and the induction of host defense peptides (defensins and cathelicidins), acute phase proteins and complement activation. As an alternative to antibiotics, innate immune mechanisms are highly relevant as they offer rapid general ways to, at least partially, protect against infections and enable the build-up of a sufficient adaptive immune response...
July 31, 2018: Veterinary Research
Valeria Castelletto, Ruth H Barnes, Kimon-Andreas Karatzas, Charlotte J C Edwards-Gayle, Francesca Greco, Ian W Hamley, Jani Seitsonen, Janne Ruokolainen
We study the self-assembly of arginine-capped bolaamphiphile peptide RA3 R (A: alanine, R: arginine) together with its binding to model membranes and its cytotoxicity and antimicrobial activity. Anionic 2-oleoyl-1-palmitoyl- sn-glycero-3-phospho-rac-(1-glycerol) sodium salt/2-oleoyl-1-palmitoyl- sn-glycero-3-phosphoethanolamine (POPG/POPE) vesicles and zwitterionic 1,2-dioleoyl- sn-glycero-3-phosphocholine/2-oleoyl-1-palmitoyl- sn-glycero-3-phosphocholine (POPC/DOPC) vesicles are used as model membranes to mimic bacterial and mammalian cell membranes, respectively...
August 13, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Ping He, Eryn K Matich, Lance T Yonkos, Alan E Friedman, G Ekin Atilla-Gokcumen, Diana S Aga
The identification of myriad of chemicals in the environment that mimic hormones and affect the endocrine functions of exposed organism is a daunting analytical challenge for environmental scientists and engineers. Many of these endocrine disrupting chemicals (EDCs) are present at very low concentrations in the aquatic systems, but yet affect the metabolic, developmental, and reproductive functions in exposed fish and wildlife. Vitellogenin (VTG) protein is a widely used biomarker in fish for assessing exposure to EDCs, and is commonly measured using species-specific immunochemical techniques...
July 25, 2018: Science of the Total Environment
Alif Meem Nurani, Yuki Kondo, Hiroo Fukuda
Vascular system is vital for the transport of water and nutrients as well as for providing mechanical support in many land plants. Plant transcription factors play a central role in regulating vascular development downstream of hormones and peptide signaling pathways. Particularly, cell culture systems have contributed to isolating such key transcription factors for xylem differentiation. However, there had been no efficient systems that can mimic phloem differentiation in the model plant Arabidopsis, preventing the identification of phloem-related transcription factors...
2018: Methods in Molecular Biology
Amira Namsi, Thomas Nury, Haithem Hamdouni, Aline Yammine, Anne Vejux, Dominique Vervandier-Fasseur, Norbert Latruffe, Olfa Masmoudi-Kouki, Gérard Lizard
In the prevention of neurodegeneration associated with aging and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), neuronal differentiation is of interest. In this context, neurotrophic factors are a family of peptides capable of promoting the growth, survival, and/or differentiation of both developing and immature neurons. In contrast to these peptidyl compounds, polyphenols are not degraded in the intestinal tract and are able to cross the blood⁻brain barrier. Consequently, they could potentially be used as therapeutic agents in neurodegenerative pathologies associated with neuronal loss, thus requiring the stimulation of neurogenesis...
July 22, 2018: Diseases (Basel)
Zijun Bie, Rongrong Xing, Xinpei He, Yanyan Ma, Yang Chen, Zhen Liu
Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches. However, due to their low immunogenicity and poor availability, glycans pose serious challenges to antibody development. Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare. Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs...
August 2, 2018: Analytical Chemistry
Hideo Ohuchi, Jun Negishi, Hikari Miike, Yuka Toyoshima, Hitomi Morimoto, Midori Fukuyama, Toru Iwasa, Heima Sakaguchi, Aya Miyazaki, Isao Shiraishi, Kenichi Kurosaki, Michikazu Nakai
OBJECTIVE: Exercise training is recommended for its possible favorable effects on Fontan pathophysiology. This study aimed to elucidate the impact of pediatric exercise capacity trajectory, which may mimic the effect of exercise training, on late adult Fontan pathophysiology. METHODS: Since 1990, 97 Fontan patients had consecutively undergone two serial cardiopulmonary exercise tests (CPX1 and CPX2) during childhood (ages 8 ± 2 and 14 ± 2 years) and one during adulthood (CPX3; age 23 ± 5 years)...
July 4, 2018: International Journal of Cardiology
Stephanie Santarriaga, Holly N Haver, Adam J Kanack, Alicia S Fikejs, Samantha L Sison, John M Egner, Jonathan R Bostrom, Emily R Seminary, R Blake Hill, Brian A Link, Allison D Ebert, K Matthew Scaglione
The polyglutamine (polyQ) diseases are a group of nine neurodegenerative diseases caused by the expansion of a polyQ tract that results in protein aggregation. Unlike other model organisms, Dictyostelium discoideum is a proteostatic outlier, naturally encoding long polyQ tracts yet resistant to polyQ aggregation. Here we identify serine-rich chaperone protein 1 (SRCP1) as a molecular chaperone that is necessary and sufficient to suppress polyQ aggregation. SRCP1 inhibits aggregation of polyQ-expanded proteins, allowing for their degradation via the proteasome, where SRCP1 is also degraded...
July 19, 2018: Molecular Cell
Simon M Bryant, Cherrie H T Kong, Judy J Watson, Hanne C Gadeberg, David M Roth, Hemal H Patel, Mark B Cannell, Andrew F James, Clive H Orchard
Caveolin-3 (Cav-3) is a protein that has been implicated in t-tubule formation and function in cardiac ventricular myocytes. In cardiac hypertrophy and failure, Cav-3 expression decreases, t-tubule structure is disrupted and excitation-contraction coupling (ECC) is impaired. However, the extent to which the decrease in Cav-3 expression underlies these changes is unclear. We therefore investigated the structure and function of myocytes isolated from the hearts of Cav-3 KO mice. These mice showed cardiac dilatation and decreased ejection fraction in vivo, compared to WT controls...
July 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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