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Xiaolei Gu, Min Qiu, Huanli Sun, Jian Zhang, Liang Cheng, Chao Deng, Zhiyuan Zhong
Despite the great significance of clinically viable nanovehicles, very few of them exhibit stability and high anticancer drug loading with fast intracellular drug release. Herein, we report that polytyrosine nanoparticles (PTNs) self-assembled from poly(ethylene glycol)-b-poly(l-tyrosine) block copolymer enable the ultra-high loading and rapid enzyme-responsive release of doxorubicin (DOX). Notably, PTNs achieve a remarkably high DOX loading of 63.1 wt% likely due to the existence of strong π-π stacking between polytyrosine and DOX, as shown by UV-vis analysis...
April 18, 2018: Biomaterials Science
Rajendra Aluri, Sonashree Saxena, Dheeraj Chandra Joshi, Manickam Jayakannan
Multi-stimuli-responsive L-tyrosine based amphiphilic poly(ester-urethane)s nano-carriers were designed and developed, for the first time, to administrate anticancer drugs at cancer tissue environment via thermo-responsiveness and lysosomal enzymatic-biodegradation from single polymer platform. For this purpose, multifunctional L-tyrosine monomer was tailor-made with PEG-lated side chain at the phenolic position along with urethane and carboxylic ester functionalities. Under melt dual ester-urethane polycondensation, the tyrosine-monomer reacted with diols to produce high molecular weight amphiphilic poly(ester-urethane)s...
April 17, 2018: Biomacromolecules
Hiep Khong, Annika Volmari, Meenu Sharma, Zhimin Dai, Chinonye S Imo, Yared Hailemichael, Manisha Singh, Derek T Moore, Zhilan Xiao, Xue-Fei Huang, Thomas D Horvath, David H Hawke, Willem W Overwijk
Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that an excessively long duration of Ag presentation critically reduced the quantity and quality of vaccination-induced T cell responses and subsequent antitumor efficacy. In this study, using a murine model and tumor cell lines, we studied l-tyrosine amino acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag depot function for the induction of tumor-specific T cells...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Dong Xu Lan, Xi Chen, Pengcheng Li, Wei Zou, Lili Wu, Wanyu Chen
The storage of living cells is the major challenge for cell research and cell treatment. Here, we introduced a novel supramolecular gel cryopreservation system which was prepared in microchannel and the supramolecular gel (BDTC) was self-assembled by gelator Boc-O-dodecyl-L-tyrosine (BDT). This cryopreservation system could obviously minimize the cell injury because BDTC supramolecular gel had a more compact three-dimensional network structure when BDT gelator self-assembled in the confined space of microchannel...
April 9, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Müslüm Kuzu, Veysel Çomaklı, Ebru Akkemik, Mehmet Çiftci, Ömer İrfan Küfrevioğlu
In this study, CA I and II isoenzymes were purified from Van Lake fish gills by using Sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography and to determine the effects of some metals on the enzyme activities. For purified CA I isoenzyme, yield, specific activity, and purification fold were obtained as 42.07%, 4948.12 EU/mg protein, and 116.61 and for CA II isoenzyme, 7%, 1798.56 EU/mg protein, and 42.38 respectively. Activity of CA was determined by measuring "CO2 -hydratase activity". Purity control was checked by SDS-PAGE...
April 8, 2018: Fish Physiology and Biochemistry
Asma Bashir, Jannick Brennum, Helle Broholm, Ian Law
OBJECTIVE The diagnostic accuracy of O-(2-[18 F]fluoroethyl)-l-tyrosine (FET) PET scanning in detecting the malignant transformation of low-grade gliomas (LGGs) is controversial. In this study, the authors retrospectively assessed the diagnostic potential of FET PET in patients with MRI-suspected malignant progression of LGGs that had previously been treated and the relationship between FET uptake and MRI and molecular biomarkers. METHODS Forty-two patients who had previously undergone surgical or multimodal treatment for a histologically verified LGG were referred for FET PET assessment because of clinical signs and/or MRI findings suggestive of tumor progression...
April 6, 2018: Journal of Neurosurgery
Sorour Hassani, Behzad Gharechaei, Somayeh Nikfard, Mostafa Fazli, Nematollah Gheibi, Renaud Hardré, Raymond L Legge, Kamahldin Haghbeen
Kinetics studies of L-tyrosine (LTy) ortho-hydroxylation by mushroom tyrosinase (MT) confirmed that MT was severely, but not completely, inhibited at higher concentrations of LTy. Despite the availability of the crystal structure reports, no allosteric site has been identified on MT. To examine the assumption that a non-specific binding site works as a regulatory site, docking simulations were run for the second molecule of L-tyrosine (LTy2 ) on the complexes of the first L-tyrosine molecule (LTy1 ) with the heavy chain (H) of MT (LTy1 /HMT) and its dimer with the light chain (Ty1 /LHMT)...
April 2, 2018: International Journal of Biological Macromolecules
Nanxi Wang, Bing Yang, Caiyun Fu, He Zhu, Feng Zheng, Tomonori Kobayashi, Jun Liu, Shanshan Li, Cheng Ma, Peng George Wang, Qian Wang, Lei Wang
Introducing new chemical reactivity into proteins in living cells would endow innovative covalent bonding ability to proteins for research and engineering in vivo. Latent bioreactive unnatural amino acids (Uaas) can be incorporated into proteins to react with target natural amino acid residues via proximity-enabled reactivity. To expand the diversity of proteins amenable to such reactivity in vivo, a chemical functionality that is biocompatible and able to react with multiple natural residues under physiologi-cal conditions is highly desirable...
March 30, 2018: Journal of the American Chemical Society
Cynthia K Holland, Joseph M Jez
Unlike metazoans, plants, bacteria, and fungi retain the enzymatic machinery necessary to synthesize the three aromatic amino acids, L¬-phenylalanine, L-tyrosine, and L-tryptophan de novo. In legumes, such as soybean, alfalfa, and common bean, prephenate dehydrogenase (PDH) catalyzes the tyrosine-insensitive biosynthesis of 4-hydroxyphenylpyruvate, a precursor to tyrosine. The three-dimensional structure of soybean PDH1 was recently solved in complex with the NADP+ cofactor. This structure allowed for the identification of both the cofactor- and ligand-binding sites...
March 30, 2018: Chembiochem: a European Journal of Chemical Biology
Mehdi Taslimifar, Stefano Buoso, Francois Verrey, Vartan Kurtcuoglu
The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available in vitro and in vivo standard methods so far...
2018: Frontiers in Physiology
Annike Weißenstein, Chantu R Saha-Möller, Frank Würthner
We have studied the host-guest binding properties of a crown ether equipped, fluorescent perylene bisimide (PBI) receptor with a series of aromatic amino acids and dipeptides by UV/Vis, fluorescence and NMR spectroscopy. Fluorescence titration experiments showed that electron-rich aromatic amino acids L-tryptophan (L-Trp) and L-tyrosine (L-Tyr) as well as dipeptides containing these amino acids strongly quench the fluorescence of the electron-poor PBI molecule. Benesi-Hildebrand plots of fluorescence titration data confirmed the formation of host-guest complexes with 1:2 stoichiometry...
March 25, 2018: Chemistry: a European Journal
Joeri De Cloet, Stephanie Van Biervliet, Myriam Van Winckel
OBJECTIVE: Because there are almost no standard all-in-one parenteral nutrition admixtures available for infants and children, the aim was to develop standard two-compartment parenteral nutrition bags for different weight categories based on the ESPGHAN/ESPEN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition/European Society for Clinical Nutrition and Metabolism) guidelines. The 1 g/kg/d lipid version for the 3 to 10 kg weight category (PED1) was assessed for short- and long-term physicochemical stability with the ability to add additional electrolytes (PED1+E)...
May 2018: Nutrition
Arleta Rifati Nixha, Adem Ergun, Nahit Gencer, Oktay Arslan, Mustafa Arslan
Polyphenol oxidase (Tyrosinase, PPO) has received considerable attention, since it is the key enzyme in melanin biosynthesis. In this study, we investigated prepared novel carbazole-containing pyridopyrimidine-substituted with urea and thiourea derivatives and their PPO activities on the diphenolase activity of banana tyrosinase. The structures of the compounds synthesized were confirmed by 1 H NMR, 13 C NMR, FTIR and elemental analysis. PPO enzyme was purified from banana on an affinity gel comprised of Sepharose 4B-L-tyrosine-p-amino benzoic acid...
March 23, 2018: Archives of Physiology and Biochemistry
Kambiz Varmira, Ghobad Mohammadi, Majid Mahmoudi, Reza Khodarahmi, Khodabakhsh Rashidi, Mehdi Hedayati, Hector C Goicoechea, Ali R Jalalvand
In this work, fabrication of a novel and ultrasensitive electrochemical biosensor based on immobilization of tyrosine hydroxylase onto palladium-platinum bimetallic alloy nanoparticles/chitosan-1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide/graphene-multiwalled carbon nanotubes-IL/glassy carbon electrode for determination of L-tyrosine in some high tyrosine foods including cheese, egg and yogurt was reported. Immobilization of tyrosine hydroxylase onto the surface of the biosensor was performed by cross-linking tyrosine hydroxylase and chitosan through the addition of glutaraldehyde...
June 1, 2018: Talanta
Garry Ceccon, Lazaros Lazaridis, Gabriele Stoffels, Marion Rapp, Manuel Weber, Tobias Blau, Phillip Lohmann, Sied Kebir, Ken Herrmann, Gereon R Fink, Karl-Josef Langen, Martin Glas, Norbert Galldiks
PURPOSE: We present our first clinical experience with O-(2-18 F-fluoroethyl)-L-tyrosine (FET) PET in patients with high-grade glioma treated with various neurooncological therapies including tumour-treating fields (TTFields) for the differentiation of tumour progression from treatment-related changes. METHODS: We retrospectively assessed 12 patients (mean age 51 ± 12 years, range 33-72 years) with high-grade glioma (11 glioblastomas, 1 gliosarcoma) in whom the treatment regimen included TTFields and who had undergone FET PET scans for differentiation of tumour progression from treatment-related changes...
March 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Ana Rita Lima, Ana Margarida Araújo, Joana Pinto, Carmen Jerónimo, Rui Henrique, Maria de Lourdes Bastos, Márcia Carvalho, Paula Guedes de Pinho
Prostate cancer (PCa) is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA) has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography-mass spectrometry (GC-MS) based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR) expression, DU145 and PC3 (which lack AR expression), and one normal prostate cell line (PNT2)...
March 19, 2018: Metabolites
Bingbing Hou, Liyuan Tao, Xiaoyu Zhu, Wei Wu, Meijin Guo, Jiang Ye, Haizhen Wu, Huizhan Zhang
Global regulator BldA, the only tRNA for a rare leucine codon UUA, is best known for its ability to affect morphological differentiation and secondary metabolism in the genus Streptomyces. In this study, we confirmed the regulatory function of the bldA gene (Genbank accession no. EU124663.1) in Streptomyces lincolnensis. Disruption of bldA hinders the sporulation and lincomycin production, that can recur when complemented with a functional bldA gene. Western blotting assays demonstrate that translation of the lmbB2 gene which encodes a L-tyrosine hydroxylase is absolutely dependent on BldA; however, mistranslation of the lmbU gene which encodes a cluster-situated regulator (CSR) is observed in a bldA mutant...
March 17, 2018: Applied Microbiology and Biotechnology
Anirban Roy, Robert Seidel, Gaurav Kumar, Stephen E Bradforth
Direct measurements of the valence ionization energies and the reorganization energies of the three aromatic amino acids, L-Tyrosine, L-Tryptophan, and L-Phenylalanine in aqueous solution using the liquid microjet technique and two different photoemission methods - X-ray photoelectron spectroscopy (XPS) at 175 eV photon energy and resonant two-photon ionization (R2PI) using 2 x 267 nm (2 x 4.64 eV) UV laser light are reported. L-Tryptophan has the lowest vertical ionization energy, 7.3 eV, followed by Tyrosine (7...
March 12, 2018: Journal of Physical Chemistry. B
Tanja Scherer, Gabriella Allegri, Christineh N Sarkissian, Ming Ying, Hiu Man Grisch-Chan, Anahita Rassi, Shelley R Winn, Cary O Harding, Aurora Martinez, Beat Thöny
Hyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH4 ) treatment in Pahenu1/enu2 (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type...
March 8, 2018: Journal of Inherited Metabolic Disease
J Janata, Z Kamenik, R Gazak, S Kadlcik, L Najmanova
Covering: up to 2017This review covers the biosynthetic and evolutionary aspects of lincosamide antibiotics, antitumour pyrrolobenzodiazepines (PBDs) and the quorum-sensing molecule hormaomycin. These structurally and functionally diverse groups of complex natural products all incorporate rarely occurring 4-alkyl-l-proline derivatives (APDs) biosynthesized from l-tyrosine through an unusual specialized pathway catalysed by a common set of six proteins named Apd1-Apd6. We give an overview of APD formation, which involves unusual enzyme activities, and its incorporation, which is based either on nonribosomal peptide synthetase (PBDs, hormaomycin) or a unique hybrid ergothioneine-dependent condensation system followed by mycothiol-dependent sulphur atom incorporation (lincosamides)...
March 8, 2018: Natural Product Reports
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