152 results match your criteria depleting arginine

Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation.

Cell Rep 2021 May;35(6):109101

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase, but it is unclear how these cancers, but not T cells, tolerate arginine depletion. In this study, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Read More

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Constitutive nitric oxide synthase-like enzyme in two species involved in cutaneous and mucocutaneous leishmaniasis.

Parasitol Int 2021 Aug 19;83:102347. Epub 2021 Apr 19.

Federal University of Para, Institute of Biological Sciences, Laboratory of Structural Biology, Belém 66095-110, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, 21.941-902 Rio de Janeiro, Brazil. Electronic address:

Leishmania is an obligate intracellular parasite that primarily inhabits macrophages. The destruction of the parasite in the host cell is a fundamental mechanism for infection control. In addition, inhibition of the leishmanicidal activity of macrophages seems to be related to the ability of some species to inhibit the production of nitric oxide (NO) by depleting arginine. Read More

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A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma.

Invest New Drugs 2021 Apr 15. Epub 2021 Apr 15.

Department of Anatomical and Cellular Pathology|, The Chinese University of Hong Kong, Hong Kong, China.

Background: Pegylated recombinant human arginase (PEG-BCT-100) is an arginine depleting drug. Preclinical studies showed that HCC is reliant on exogenous arginine for growth due to the under-expression of the arginine regenerating enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC).

Methods: This is a single arm open-label Phase II trial to assess the potential clinical efficacy of PEG-BCT-100 in chemo naïve sorafenib-failure HCC patients. Read More

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Evidence of an antidepressant-like effect of xylopic acid mediated by serotonergic mechanisms.

Psychopharmacology (Berl) 2021 Apr 10. Epub 2021 Apr 10.

Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana.

Background: Depression causes significant debilitating symptoms and economic burden. Current management is challenged by slow onset of action and modest efficacies of antidepressants; thus, the search for newer antidepressants remains relevant. We evaluated the antidepressant effects of a kaurene diterpene, xylopic acid (XA), in zebrafish and mouse models. Read More

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Histone deacetylases control lysine acetylation of ribosomal proteins in rice.

Nucleic Acids Res 2021 05;49(8):4613-4628

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, 430070 Wuhan, China.

Lysine acetylation (Kac) is well known to occur in histones for chromatin function and epigenetic regulation. In addition to histones, Kac is also detected in a large number of proteins with diverse biological functions. However, Kac function and regulatory mechanism for most proteins are unclear. Read More

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Arginase 1 Insufficiency Precipitates Amyloid- Deposition and Hastens Behavioral Impairment in a Mouse Model of Amyloidosis.

Front Immunol 2020 14;11:582998. Epub 2021 Jan 14.

Sanders-Brown Center on Aging, Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, United States.

Alzheimer's disease (AD) includes several hallmarks comprised of amyloid- (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. Read More

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January 2021

Depleting deubiquitinating enzymes promotes apoptosis in glioma cell line via RNA binding proteins SF2/ASF1.

Biochem Biophys Rep 2020 Dec 8;24:100846. Epub 2020 Dec 8.

Cancer Genetics Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Delhi, 110007, India.

USP5 and USP8 (Deubiquitinating enzyme) are highly overexpressed and more recognized as poor prognosis marker in various cancers. Depleting USP5 or USP8 to assess the synergism with proteasome inhibitor (Bortezomib) were measured. Furthermore, in present finding USP5 cooperates hnRNPA1 & USP8 cooperate SF2/ASF1, therefore gain in expression of either hnRNPA1 or SF2/ASF1 is sufficient to promote cell survival. Read More

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December 2020

Rational design, engineer, and characterization of a novel pegylated single isomer human arginase for arginine depriving anti-cancer treatment.

Life Sci 2021 Jan 28;264:118674. Epub 2020 Oct 28.

State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology and Lo Ka Chung Research Centre for Natural Anti-Cancer Drug, The Hong Kong Polytechnic University, Hong Kong.

Aims: Arginine depleting enzymes are found effective to treat arginine-auxotrophic cancers and therapy-resistant malignancies, alone or in combination with cytotoxic agents or immune checkpoint inhibitors. We aim to select and validate a long-lasting, safe and effective PEGylated and cobalt-chelated arginase conjugated at the selective cysteine residue as a therapeutic agent against cancers.

Main Methods: Exploring pharmacokinetic and pharmacodynamic properties of the three arginase conjugates with different PEG modality (20 kDa linear as A20L, 20 kDa branched as A20Y, and 40 kDa branched as A40Y) by cell-based and animal studies. Read More

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January 2021

SON and SRRM2 are essential for nuclear speckle formation.

Elife 2020 10 23;9. Epub 2020 Oct 23.

Max Planck Institute for Molecular Genetics, Berlin, Germany.

Nuclear speckles (NS) are among the most prominent biomolecular condensates. Despite their prevalence, research on the function of NS is virtually restricted to colocalization analyses, since an organizing core, without which NS cannot form, remains unidentified. The monoclonal antibody SC35, raised against a spliceosomal extract, is frequently used to mark NS. Read More

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October 2020

Systems level profiling of arginine starvation reveals MYC and ERK adaptive metabolic reprogramming.

Cell Death Dis 2020 08 20;11(8):662. Epub 2020 Aug 20.

Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, 63110, USA.

Arginine auxotrophy due to the silencing of argininosuccinate synthetase 1 (ASS1) occurs in many carcinomas and in the majority of sarcomas. Arginine deiminase (ADI-PEG20) therapy exploits this metabolic vulnerability by depleting extracellular arginine, causing arginine starvation. ASS1-negative cells develop resistance to ADI-PEG20 through a metabolic adaptation that includes re-expressing ASS1. Read More

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host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration.

Sci Signal 2020 07 21;13(641). Epub 2020 Jul 21.

Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

is implicated in accelerating colorectal cancer (CRC) and is found within metastatic CRC cells in patient biopsies. Here, we found that bacterial invasion of CRC cells and cocultured immune cells induced a differential cytokine secretion that may contribute to CRC metastasis. We used a modified galactose kinase markerless gene deletion approach and found that invaded cultured HCT116 CRC cells through the bacterial surface adhesin Fap2. Read More

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Mono-PEGylation of a Thermostable Arginine-Depleting Enzyme for the Treatment of Lung Cancer.

Int J Mol Sci 2020 Jun 14;21(12). Epub 2020 Jun 14.

Department of Applied Biology and Chemical Technology, Lo Ka Chung Research Centre for Natural Anti-Cancer Drug Development and State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.

L-arginine (L-Arg) depletion induced by randomly PEGylated arginine deiminase (ADI-PEG20) can treat arginosuccinate synthase (ASS)-negative cancers, and ADI-PEG20 is undergoing phase III clinical trials. Unfortunately, ASS-positive cancers are resistant to ADI-PEG20. Moreover, the yield of ADI production is low because of the formation of inclusion bodies. Read More

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A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells.

PLoS One 2020 30;15(4):e0231633. Epub 2020 Apr 30.

State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology and Lo Ka Chung Research Centre for Natural Anti-Cancer Drug Development, The Hong Kong Polytechnic University, Hong Kong, China.

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Read More

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Naringin protects against Bisphenol-A induced oculopathy as implication of cataract in hypertensive rat model.

Biomed Pharmacother 2020 Jun 13;126:110043. Epub 2020 Mar 13.

Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Nigeria.

People who have experienced high blood pressure are at greater risk of susceptibility to other health problems including oculopathy. The patients with these experiences do not have adequate treatment and those who do; spend much funds on the drug purchase. The study examines the protective effect of naringin (NRG) against ocular impairment in -NAME induced hypertensive rat on exposure to a cellular disruptor. Read More

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A bioengineered arginine-depleting enzyme as a long-lasting therapeutic agent against cancer.

Appl Microbiol Biotechnol 2020 May 6;104(9):3921-3934. Epub 2020 Mar 6.

Department of Applied Biology and Chemical Technology, Lo Ka Chung Research Centre for Natural Anti-Cancer Drug Development and State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.

L-Arginine (L-Arg) depletion has attracted great attention in cancer therapy. Although two types of arginine-depleting enzymes, arginine deiminase (ADI) and human arginase I, are undergoing clinical trials, random site of PEGylation, low efficacy of heavy metal as co-factor, and immunogenicity limit the performance of these drugs and cause difficulty in a homogeneous production. Here we screened ten catalytic metal ions and have successfully produced a site-specific mono-PEGylated human arginase I mutant by conjugating the Cys residue to PEG-maleimide to minimize the decrease in activity and produce a homogeneous product. Read More

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Microbial enzymes for deprivation of amino acid metabolism in malignant cells: biological strategy for cancer treatment.

Appl Microbiol Biotechnol 2020 Apr 10;104(7):2857-2869. Epub 2020 Feb 10.

Medical Microbiology and Bioprocess Technology Laboratory, Department of Microbiology, Maharshi Dayanand University, Rohtak, Haryana, India.

Amino acid deprivation therapy (AADT) is emerging as a promising strategy for the development of novel therapeutics against cancer. This biological therapy relies upon the differences in the metabolism of cancer and normal cells. The rapid growth of tumors results in decreased expression of certain enzymes leading to auxotrophy for some specific amino acids. Read More

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Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells.

J Exp Clin Cancer Res 2019 Oct 10;38(1):414. Epub 2019 Oct 10.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China.

Background: Tamoxifen resistance presents a huge clinical challenge for breast cancer patients. An understanding of the mechanisms of tamoxifen resistance can guide development of efficient therapies to prevent drug resistance.

Methods: We first tested whether peptidylarginine deiminase 2 (PAD2) may be involved in tamoxifen-resistance in breast cancer cells. Read More

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October 2019

The Short N-Terminal Repeats of Transcription Termination Factor 1 Contain Semi-Redundant Nucleolar Localization Signals and P19-ARF Tumor Suppressor Binding Sites.

Yale J Biol Med 2019 09 20;92(3):385-396. Epub 2019 Sep 20.

Laboratory of Growth and Development, St-Patrick Research Group in Basic Oncology, Cancer Division of the Quebec University Hospital Research Centre (Axe Cancer, CR-CHU de Québec), Quebec, QC, Canada.

The p14/p19 (ARF) tumor suppressor provides an important link in the activation of p53 (TP53) by inhibiting its targeted degradation via the E3 ligases MDM2/HDM2. However, ARF also limits tumor growth by directly inhibiting ribosomal RNA synthesis and processing. Initial studies of the ARF tumor suppressor were compounded by overlap between the INK4A and ARF genes encoded by the CDKN2A locus, but mouse models of pure ARF-loss and its inactivation in human cancers identified it as a distinct tumor suppressor even in the absence of p53. Read More

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September 2019

Arginase enzymes in the human prostate: A molecular biological and immunohistochemical approach.

Andrologia 2019 Oct 10;51(9):e13349. Epub 2019 Jul 10.

Department of Urology & Urological Oncology, Division of Surgery, Hannover Medical School, Hannover, Germany.

The nitric oxide (NO) pathway plays a role in maintaining the function of the prostate. An impairment in the activity of the NO system may have an impact in the manifestation of lower urinary tract symptomatology and benign prostatic hyperplasia. Arginase enzymes (Arg) counteract the generation of NO by depleting the intracellular pool of L-arginine, known to be the substrate of the NO synthases. Read More

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October 2019

Amino acid metabolism in hematologic malignancies and the era of targeted therapy.

Blood 2019 09 15;134(13):1014-1023. Epub 2019 Aug 15.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.

Tumor cells rewire metabolic pathways to adapt to their increased nutritional demands for energy, reducing equivalents, and cellular biosynthesis. Alternations in amino acid metabolism are 1 modality for satisfying those demands. Amino acids are not only components of proteins but also intermediate metabolites fueling multiple biosynthetic pathways. Read More

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September 2019

Exploiting Arginine Auxotrophy with Pegylated Arginine Deiminase (ADI-PEG20) to Sensitize Pancreatic Cancer to Radiotherapy via Metabolic Dysregulation.

Mol Cancer Ther 2019 12 8;18(12):2381-2393. Epub 2019 Aug 8.

Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.

Distinct metabolic vulnerabilities of cancer cells compared with normal cells can potentially be exploited for therapeutic targeting. Deficiency of argininosuccinate synthetase-1 (ASS1) in pancreatic cancers creates auxotrophy for the semiessential amino acid arginine. We explored the therapeutic potential of depleting exogenous arginine via pegylated arginine deiminase (ADI-PEG20) treatment as an adjunct to radiotherapy. Read More

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December 2019

cRGD-decorated biodegradable polytyrosine nanoparticles for robust encapsulation and targeted delivery of doxorubicin to colorectal cancer in vivo.

J Control Release 2019 05 18;301:110-118. Epub 2019 Mar 18.

Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. Electronic address:

The clinical success of nanomedicines demands on the development of simple biodegradable nanocarriers that can efficiently and stably encapsulate chemotherapeutics while quickly release the payloads into target cancer cells. Herein, we report that cRGD-decorated biodegradable polytyrosine nanoparticles (cRGD-PTN) boost encapsulation and targeted delivery of doxorubicin (DOX) to colorectal cancer in vivo. The co-assembly of poly(ethylene glycol)-poly(L-tyrosine) (PEG-PTyr) and cRGD-functionalized PEG-PTyr (mol/mol, 80/20) yielded small-sized cRGD-PTN of 70 nm. Read More

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Substantial Extracellular Metabolic Differences Found Between Phylogenetically Closely Related Probiotic and Pathogenic Strains of .

Front Microbiol 2019 19;10:252. Epub 2019 Feb 19.

Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, United Kingdom.

Since its first isolation a century ago, the gut inhabitant strain Nissle 1917 has been shown to have probiotic activities; however, it is yet not fully elucidated which differential factors play key roles in its beneficial interactions with the host. To date, no metabolomics studies have been reported investigating the potential role of small molecules in functional strain differentiation of Nissle from its genetically close neighbors. Here, we present results of liquid chromatography coupled to high-resolution mass spectrometry characterization of extracellular metabolomes of strains as a proxy of their bioactivity potential. Read More

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February 2019

Arginine-Depleting Enzymes - An Increasingly Recognized Treatment Strategy for Therapy-Refractory Malignancies.

Cell Physiol Biochem 2018 22;51(2):854-870. Epub 2018 Nov 22.

Department of Medicine, Clinic III-Hematology/ Oncology/Palliative Care, Rostock University Medical Center, University of Rostock, Rostock,

Arginine auxotrophy occurs in certain tumor types and is usually caused by the silencing of argininosuccinate synthetase 1 or arginine lyase genes. Such tumors are often associated with an intrinsic chemoresistance and thus a poor prognosis. Arginine auxotrophy however renders these tumors vulnerable to treatment with arginine-degrading enzymes. Read More

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December 2018

Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction.

Commun Biol 2018 26;1:178. Epub 2018 Oct 26.

Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA, 91010, USA.

Defective arginine synthesis, due to the silencing of (ASS1), is a common metabolic vulnerability in cancer, known as arginine auxotrophy. Understanding how arginine depletion kills arginine-auxotrophic cancer cells will facilitate the development of anti-cancer therapeutic strategies. Here we show that depletion of extracellular arginine in arginine-auxotrophic cancer cells causes mitochondrial distress and transcriptional reprogramming. Read More

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October 2018

Enzyme-immobilized metal-organic framework nanosheets as tandem catalysts for the generation of nitric oxide.

Chem Commun (Camb) 2018 Oct;54(79):11176-11179

Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Key Laboratory of Chemo/Biosensing, Laboratory of Optical Probes and Bioelectrocatalysis (LOPAB), College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, P. R. China.

An enzyme-immobilized metal-organic framework (MOF) nanosheet system was developed as a tandem catalyst, which converted glucose into gluconic acid and H2O2, and sequentially the latter could be used to catalyze the oxidation of l-arginine to generate nitric oxide in the presence of porphyrinic MOFs as artificial enzymes under physiological pH, showing great potential in cancer depleting glucose for starving-like/gas therapy. Read More

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October 2018

Inhibition of ornithine decarboxylase 1 facilitates pegylated arginase treatment in lung adenocarcinoma xenograft models.

Oncol Rep 2018 Oct 25;40(4):1994-2004. Epub 2018 Jul 25.

Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, SAR, P.R. China.

Arginine depletion has shown anticancer effects among arginine auxotrophic cancers. An anti‑proliferative effect of pegylated arginase (BCT‑100) has been shown in acute myeloid leukaemia, hepatocellular carcinoma and mesothelioma. The aim of the present study was to evaluate the effect of BCT‑100 in lung adenocarcinoma. Read More

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October 2018

Rac1 Nanoscale Organization on the Plasma Membrane Is Driven by Lipid Binding Specificity Encoded in the Membrane Anchor.

Mol Cell Biol 2018 09 28;38(18). Epub 2018 Aug 28.

Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA

Rac1 is a small guanine nucleotide binding protein that cycles between an inactive GDP-bound and active GTP-bound state to regulate cell motility and migration. Rac1 signaling is initiated from the plasma membrane (PM). Here, we used high-resolution spatial mapping and manipulation of PM lipid composition to define Rac1 nanoscale organization. Read More

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September 2018

Biochemical and biophysical insights into the metal binding spectrum and bioactivity of arginase of Entamoeba histolytica.

Metallomics 2018 04;10(4):623-638

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

The human protozoan pathogens possess the essential metalloenzyme arginase (Arg) which catalyses the catabolism of l-arginine to l-ornithine and urea. This being the first committed step in polyamine biosynthesis is a potential drug target for protozoan diseases. In pathogenic organisms, arginase plays a crucial role in depleting host l-arginine, a substrate for nitric oxide synthase (NOS) that participates in protective immunity, thereby evading host immune response. Read More

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Decreasing the immunogenicity of arginine deiminase enzyme via structure-based computational analysis.

J Biomol Struct Dyn 2019 Feb 7;37(2):523-536. Epub 2018 Feb 7.

a Department of Pharmaceutical Biotechnology, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz , Iran.

The clinical applications of therapeutic enzymes are often limited due to their immunogenicity. B-cell epitope removal is an effective approach to solve this obstacle. The identification of hot spot epitopic residues is a critical step in the removal of protein B-cell epitope. Read More

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February 2019