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https://www.readbyqxmd.com/read/28916756/identification-of-the-s100-fused-type-protein-hornerin-as-a-regulator-of-tumor-vascularity
#1
Michael F Gutknecht, Marc E Seaman, Bo Ning, Daniel Auger Cornejo, Emily Mugler, Patrick F Antkowiak, Christopher A Moskaluk, Song Hu, Frederick H Epstein, Kimberly A Kelly
Sustained angiogenesis is essential for the development of solid tumors and metastatic disease. Disruption of signaling pathways that govern tumor vascularity provide a potential avenue to thwart cancer progression. Through phage display-based functional proteomics, immunohistochemical analysis of human pancreatic ductal carcinoma (PDAC) specimens, and in vitro validation, we reveal that hornerin, an S100 fused-type protein, is highly expressed on pancreatic tumor endothelium in a vascular endothelial growth factor (VEGF)-independent manner...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28902178/tumor-inhibitory-effect-of-ircr201-a-novel-cross-reactive-c-met-antibody-targeting-the-psi-domain
#2
Hyunkyu Park, Donggeon Kim, Eunmi Kim, Jason K Sa, Hee Won Lee, Suji Yu, Jiwon Oh, Seok-Hyung Kim, Yeup Yoon, Do-Hyun Nam
Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28901276/immunocontraception-filamentous-bacteriophage-as-a-platform-for-vaccine-development
#3
Tatiana I Samoylova, Timothy D Braden, Jennifer A Spencer, Frank F Bartol
Population control of domestic, wild and invasive species of animals is a global issue of importance to public health, animal welfare and the economy. Although many methods for regulation of animal reproduction are available, the need for effective, safe, and inexpensive contraceptives remains. Immunocontraceptives (contraceptive vaccines) are designed to stimulate the immune system in order to block critical events in the reproductive process and suppress fertility. Platforms used for vaccine development play a critical role in vaccine efficacy, safety, and practicality...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28895936/rapid-and-highly-sensitive-non-competitive-immunoassay-for-specific-detection-of-nodularin
#4
Sultana Akter, Markus Vehniäinen, Harri T Kankaanpää, Urpo Lamminmäki
Nodularin (NOD) is a cyclic penta-peptide hepatotoxin mainly produced by Nodularia spumigena, reported from the brackish water bodies of various parts of the world. It can accumulate in the food chain and, for safety reasons, levels of NOD not only in water bodies but also in food matrices are of interest. Here, we report on a non-competitive immunoassay for the specific detection of NOD. A phage display technique was utilized to interrogate a synthetic antibody phage library for binders recognizing NOD bound to an anti-ADDA (3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E),6(E)-dienoic acid) monoclonal antibody (Mab)...
September 12, 2017: Microorganisms
https://www.readbyqxmd.com/read/28893601/seek-destroy-use-of-targeting-peptides-for-cancer-detection-and-drug-delivery
#5
Vadim Le Joncour, Pirjo Laakkonen
Accounting for 16 million new cases and 9 million deaths annually, cancer leaves a great number of patients helpless. It is a complex disease and still a major challenge for the scientific and medical communities. The efficacy of conventional chemotherapies is often poor and patients suffer from off-target effects. Each neoplasm exhibits molecular signatures - sometimes in a patient specific manner - that may completely differ from the organ of origin, may be expressed in markedly higher amounts and/or in different location compared to the normal tissue...
September 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28892521/a-systems-medicine-approach-for-finding-target-proteins-affecting-treatment-outcomes-in-patients-with-non-hodgkin-lymphoma
#6
Faezeh Ajorloo, Mohammad Vaezi, Alireza Saadat, Seyed Reza Safaee, Behrouz Gharib, Mostafa Ghanei, Seyed Davar Siadat, Farzam Vaziri, Abolfazl Fateh, Mehrdad Pazhouhandeh, Behrouz Vaziri, Reza Moazemi, Fereidoun Mahboudi, Fatemeh Rahimi Jamnani
Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28890361/comprehensive-analysis-of-the-human-sh3-domain-family-reveals-a-wide-variety-of-non-canonical-specificities
#7
Joan Teyra, Haiming Huang, Shobhit Jain, Xinyu Guan, Aiping Dong, Yanli Liu, Wolfram Tempel, Jinrong Min, Yufeng Tong, Philip M Kim, Gary D Bader, Sachdev S Sidhu
SH3 domains are protein modules that mediate protein-protein interactions in many eukaryotic signal transduction pathways. The majority of SH3 domains studied thus far act by binding to proline-rich sequences in partner proteins, but a growing number of studies have revealed alternative recognition mechanisms. We have comprehensively surveyed the specificity landscape of human SH3 domains in an unbiased manner using peptide-phage display and deep sequencing. Based on ∼70,000 unique binding peptides, we obtained 154 specificity profiles for 115 SH3 domains, which reveal that roughly half of the SH3 domains exhibit non-canonical specificities and collectively recognize a wide variety of peptide motifs, most of which were previously unknown...
August 28, 2017: Structure
https://www.readbyqxmd.com/read/28888997/discovery-of-peptide-drug-carrier-candidates-for-targeted-multi-drug-delivery-into-prostate-cancer-cells
#8
O Bashari, B Redko, A Cohen, G Luboshits, G Gellerman, M A Firer
Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated...
September 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28887476/the-c-terminal-residue-of-phage-vp16-pdf-the-smallest-peptide-deformylase-acts-as-an-offset-element-locking-the-active-conformation
#9
Renata Grzela, Julien Nusbaum, Sonia Fieulaine, Francesco Lavecchia, Willy V Bienvenut, Cyril Dian, Thierry Meinnel, Carmela Giglione
Prokaryotic proteins must be deformylated before the removal of their first methionine. Peptide deformylase (PDF) is indispensable and guarantees this mechanism. Recent metagenomics studies revealed new idiosyncratic PDF forms as the most abundant family of viral sequences. Little is known regarding these viral PDFs, including the capacity of the corresponding encoded proteins to ensure deformylase activity. We provide here the first evidence that viral PDFs, including the shortest PDF identified to date, Vp16 PDF, display deformylase activity in vivo, despite the absence of the key ribosome-interacting C-terminal region...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28886513/construction-of-genetically-engineered-m13k07-helper-phage-for-simultaneous-phage-display-of-gold-binding-peptide-1-and-nuclear-matrix-protein-22-scfv-antibody
#10
Farnaz Fatemi, Seyed Mohammad Amini, Sharmin Kharrazi, Mohammad Javad Rasaee, Mohammad Ali Mazlomi, Majid Asadi-Ghalehni, Masoumeh Rajabibazl, Esmaeil Sadroddiny
The most common techniques of antibody phage display are based on the use of M13 filamentous bacteriophages. This study introduces a new genetically engineered M13K07 helper phage displaying multiple copies of a known gold binding peptide on p8 coat proteins. The recombinant helper phages were used to rescue a phagemid vector encoding the p3 coat protein fused to the nuclear matrix protein 22 (NMP22) ScFv antibody. Transmission electron microscopy (TEM), UV-vis absorbance spectroscopy, and field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray spectroscopy (EDX) analysis revealed that the expression of gold binding peptide 1 (GBP1) on major coat protein p8 significantly enhances the gold-binding affinity of M13 phages...
August 24, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28886124/identification-and-genomic-comparison-of-temperate-bacteriophages-derived-from-emetic-bacillus-cereus
#11
Peiling Geng, Shen Tian, Zhiming Yuan, Xiaomin Hu
Cereulide-producing Bacillus cereus isolates can cause serious emetic (vomiting) syndrome and even acute lethality. As mobile genetic elements, the exploration of prophages derived from emetic B. cereus isolates will help in our understanding of the genetic diversity and evolution of these pathogens. In this study, five temperate phages derived from cereulide-producing B. cereus strains were induced, with four of them undergoing genomic sequencing. Sequencing revealed that they all belong to the Siphoviridae family, but presented in different forms in their hosts...
2017: PloS One
https://www.readbyqxmd.com/read/28884572/nanobody-based-apolipoprotein-e-immunosensor-for-point-of-care-testing
#12
Xiang Ren, Junrong Yan, Dan Wu, Qin Wei, Yakun Wan
Alzheimer's disease (AD) biomarkers can reflect the neurochemical indicators used to estimate the risk in clinical nephrology. Apolipoprotein E (ApoE) is an early biomarker for AD in clinical diagnosis. In this research, through bactrian camel immunization, lymphocyte isolation, RNA extraction, and library construction, ApoE-specific Nbs with high affinity were successfully separated from an immune phage display nanobody library. Herein, a colorimetric immunosensor was developed for the point-of-care testing of ApoE by layer-by-layer nanoassembly techniques and novel nanobodies (Nbs)...
September 11, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28884521/a-single-framework-synthetic-antibody-library-containing-a-combination-of-canonical-and-variable-complementarity-determining-regions
#13
Bharathikumar Vellalore Maruthachalam, Ayman El-Sayad, Jianghai Liu, Wayne Hill, Ashley Sutherland, Landon Pastushok, Humphrey Fonge, Kris Barreto, Clarence Ronald Geyer
Synthetic antibody libraries have been used to generate antibodies with favorable biophysical and pharmacological properties. Here, we describe the design, construction, and validation of a phage-displayed Fab library built on a modified trastuzumab framework with four fixed and two diversified complementarity-determining regions (CDRs). CDRs L1, L2, H1, and H2 were fixed to preserve the most-frequent 'canonical' CDR conformation preferred by the modified trastuzumab Fab framework. The library diversity was engineered within CDRs L3 and H3 using custom-designed trinucleotide phosphoramidite mixes and biased towards human antibody CDR sequences...
September 7, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28884285/immune-tb-antibody-phage-display-library-as-a-tool-to-study-b-cell-immunity-in-tb-infections
#14
Nurul Hamizah Hamidon, Siti Suraiya, Maria E Sarmiento, Armando Acosta, Mohd Nor Norazmi, Theam Soon Lim
B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals...
September 7, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28883821/hidden-lineage-complexity-of-glycan-dependent-hiv-1-broadly-neutralizing-antibodies-uncovered-by-digital-panning-and-native-like-gp140-trimer
#15
Linling He, Xiaohe Lin, Natalia de Val, Karen L Saye-Francisco, Colin J Mann, Ryan Augst, Charles D Morris, Parisa Azadnia, Bin Zhou, Devin Sok, Gabriel Ozorowski, Andrew B Ward, Dennis R Burton, Jiang Zhu
Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28881621/connexin40-controls-endothelial-activation-by-dampening-nf%C3%AE%C2%BAb-activation
#16
Jean-Francois Denis, K E Ludwig Scheckenbach, Anna Pfenniger, Merlijn J Meens, Rob Krams, Lucile Miquerol, Steven Taffet, Marc Chanson, Mario Delmar, Brenda R Kwak
Connexins are proteins forming gap junction channels for intercellular communication. Connexin40 (Cx40) is highly expressed by endothelial cells (ECs) of healthy arteries but this expression is lost in ECs overlying atherosclerotic plaques. Low/oscillatory shear stress observed in bends and bifurcations of arteries is atherogenic partly through activation of the pro-inflammatory NFκB pathway in ECs. In this study, we investigated the relation between shear stress, Cx40 and NFκB. Shear stress-modifying casts were placed around carotid arteries of mice expressing eGFP under the Cx40 promoter (Cx40(+/eGFP) )...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880027/tandem-wittig-diels-alder-diversification-of-genetically-encoded-peptide-libraries
#17
Vivian Triana, Ratmir Derda
In this paper, we developed a tandem of two carbon-carbon bond-forming reactions to chemically diversify the libraries of peptides displayed on a bacteriophage. The Wittig reaction of a biotin-ester from a stabilized phosphorane ylide with model peptides containing N-terminal glyoxal exhibits reaction rates of 0.07 to 5 M(-1) s(-1) in water at pH 6.5-8. The log(k) scaled linearly with pH from pH 6 to 8; above pH 9 the reaction is accompanied by the hydrolysis of the ester functionality. Capture of the phage displaying the biotinylated product by streptavidin beads confirmed the rate of this reaction in a library of 10(8) peptides (k = 0...
September 7, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28866120/identification-of-a-novel-single-chain-fragment-variable-antibody-targeting-cd24-expressing-cancer-cells
#18
Shirin Eyvazi, Bahram Kazemi, Mojgan Bandehpour, Siavoush Dastmalchi
CD24 is a heavy glycosylated protein that is overexpressed in numerous cancer and cancer stem cells. It is involved in the development, invasion, and metastasis of the cancer cells. CD24 can be considered in targeted cancer therapy as a new target. Here, phage display technology was used for the identification of novel scFv antibodies against CD24. To do so, the CD24 protein was expressed and purified from a stable transgenic CHO cell line. The cells were developed by using a CD24 encoding construct, which targets the 18S rRNA gene...
September 1, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28864568/using-phage-display-to-create-recombinant-antibodies
#19
James R Dasch, Amy L Dasch
A variety of phage display technologies have been developed since the approach was first described for antibodies. The most widely used approaches incorporate antibody sequences into the minor coat protein pIII of the nonlytic filamentous phage fd or M13. Libraries of variable gene sequences, encoding either scFv or Fab fragments, are made by incorporating sequences into phagemid vectors. The phagemid is packaged into phage particles with the assistance of a helper phage to produce the antibody display phage...
September 1, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28863269/bacteriophages-the-possible-solution-to-treat-pathogenic-bacteria
#20
Ayman El-Shibiny, Salma El-Sahhar
Bacteriophages have been used to treat bacterial infections in animals and humans since their discovery in 1915, due to their unique ability to infect their specific bacterial hosts, without affecting other bacterial populations. The research carried out in this field throughout the twentieth century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulphonamide antibiotics in the Western World during the 1930's was a setback in the advancement of phage therapy...
September 1, 2017: Canadian Journal of Microbiology
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