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https://www.readbyqxmd.com/read/27888699/tumor-detection-using-magnetosome-nanoparticles-functionalized-with-a-newly-screened-egfr-her2-targeting-peptide
#1
Zhichu Xiang, Xiaoliang Yang, Junjie Xu, Wenjia Lai, Zihua Wang, Zhiyuan Hu, Jiesheng Tian, Lingling Geng, Qiaojun Fang
A novel peptide (P75) targeting EGFR and HER2 is successfully screened from a one-bead-one-compound (OBOC) library containing approximately 2 × 10(5) peptides built with the aid of computational simulation. In vitro and in vivo analyses show that P75 binds to human epithelial growth factor receptor (EGFR) with nanomolar affinity and to epithelial growth factor receptor-2 (HER2) with a lower affinity but comparable to other reported peptides. The peptide is used to modify the surface of magnetosome nanoparticles (NPs) for targeted magnetic resonance imaging (MRI)...
November 16, 2016: Biomaterials
https://www.readbyqxmd.com/read/27812924/high-throughput-approaches-to-the-development-of-molecular-imaging-agents
#2
REVIEW
Lina Y Hu, Kimberly A Kelly, Julie L Sutcliffe
Molecular imaging allows for the visualization of changes at the cellular level in diseases such as cancer. A successful molecular imaging agent must rely on disease-selective targets and ligands that specifically interact with those targets. Unfortunately, the translation of novel target-specific ligands into the clinic has been frustratingly slow with limitations including the complex design and screening approaches for ligand identification, as well as their subsequent optimization into useful imaging agents...
November 3, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27279916/her2-targeting-peptides-screening-and-applications-in-tumor-imaging-and-drug-delivery
#3
Lingling Geng, Zihua Wang, Xiangqian Jia, Qiuju Han, Zhichu Xiang, Dan Li, Xiaoliang Yang, Di Zhang, Xiangli Bu, Weizhi Wang, Zhiyuan Hu, Qiaojun Fang
Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests...
2016: Theranostics
https://www.readbyqxmd.com/read/27257968/development-of-a-large-peptoid-dota-combinatorial-library
#4
Jaspal Singh, Daniel Lopes, D Gomika Udugamasooriya
Conventional one-bead one-compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built-in imaging component for a certain target is a daunting task, and structure-based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule...
September 2016: Biopolymers
https://www.readbyqxmd.com/read/27210583/tumor-targeting-peptides-from-combinatorial-libraries
#5
Ruiwu Liu, Xiaocen Li, Wenwu Xiao, Kit S Lam
Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides...
May 19, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/27124678/design-of-a-microfluidic-chip-for-magnetic-activated-sorting-of-one-bead-one-compound-libraries
#6
Choi-Fong Cho, Kyungheon Lee, Maria-Carmela Speranza, Fernanda C Bononi, Mariano S Viapiano, Leonard G Luyt, Ralph Weissleder, E Antonio Chiocca, Hakho Lee, Sean E Lawler
Molecular targeting using ligands specific to disease markers has shown great promise for early detection and directed therapy. Bead-based combinatorial libraries have served as powerful tools for the discovery of novel targeting agents. Screening platforms employing magnetic capture have been used to achieve rapid and efficient identification of high-affinity ligands from one-bead-one-compound (OBOC) libraries. Traditional manual methodologies to isolate magnetized "hit" beads are tedious and lack accuracy, and existing instruments to expedite bead sorting tend to be costly and complex...
June 13, 2016: ACS Combinatorial Science
https://www.readbyqxmd.com/read/27053324/rapid-discovery-of-functional-small-molecule-ligands-against-proteomic-targets-through-library-against-library-screening
#7
Chun-Yi Wu, Don-Hong Wang, Xiaobing Wang, Seth M Dixon, Liping Meng, Sara Ahadi, Daniel H Enter, Chao-Yu Chen, Jason Kato, Leonardo J Leon, Laura M Ramirez, Yoshiko Maeda, Carolina F Reis, Brianna Ribeiro, Brittany Weems, Hsing-Jien Kung, Kit S Lam
Identifying "druggable" targets and their corresponding therapeutic agents are two fundamental challenges in drug discovery research. The one-bead-one-compound (OBOC) combinatorial library method has been developed to discover peptides or small molecules that bind to a specific target protein or elicit a specific cellular response. The phage display cDNA expression proteome library method has been employed to identify target proteins that interact with specific compounds. Here, we combined these two high-throughput approaches, efficiently interrogated approximately 10(13) possible molecular interactions, and identified 91 small molecule compound beads that interacted strongly with the phage library...
June 13, 2016: ACS Combinatorial Science
https://www.readbyqxmd.com/read/26815064/h%C3%AE-sabr-photochemical-dose-response-bead-screening-in-droplets
#8
Alexander K Price, Andrew B MacConnell, Brian M Paegel
With the potential for each droplet to act as a unique reaction vessel, droplet microfluidics is a powerful tool for high-throughput discovery. Any attempt at compound screening miniaturization must address the significant scaling inefficiencies associated with library handling and distribution. Eschewing microplate-based compound collections for one-bead-one-compound (OBOC) combinatorial libraries, we have developed hνSABR (Light-Induced and -Graduated High-Throughput Screening After Bead Release), a microfluidic architecture that integrates a suspension hopper for compound library bead introduction, droplet generation, microfabricated waveguides to deliver UV light to the droplet flow for photochemical compound dosing, incubation, and laser-induced fluorescence for assay readout...
March 1, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/26778455/latest-advances-in-oboc-peptide-libraries-improvements-in-screening-strategies-and-enlarging-the-family-from-linear-to-cyclic-libraries
#9
REVIEW
Maria C Martínez-Ceron, Silvana L Giudicessi, Soledad L Saavedra, Juan M Gurevich-Messina, Rosa Erra-Balsells, Fernando Albericio, Osvaldo Cascone, Silvia A Camperi
Solid phase screenings of one bead one compound (OBOC) libraries have been widely used to find ligands with pharmacological and analytical uses, and to purify or detect proteins in complex mixtures. To improve library screening, in the last years various strategies have been developed to avoid the selection of false positive beads and to obtain selective ligands. Currently, there is great interest in cyclic peptides because of their resistance to enzymatic degradation and higher selectivity compared to their linear counterparts...
2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/26630124/covalent-chemical-ligation-strategy-for-mono-and-polyclonal-immunoglobulins-at-their-nucleotide-binding-sites
#10
Diana Lac, Chun Feng, Gaurav Bhardwaj, Huong Le, Jimmy Tran, Li Xing, Gabriel Fung, Ruiwu Liu, Holland Cheng, Kit S Lam
Nonspecific ligation methods have been traditionally used to chemically modify immunoglobulins. Site-specific ligation of compounds (toxins or ligands) to antibodies has become increasingly important in the fields of therapeutic antibody-drug conjugates and bispecific antibodies. In this present study, we took advantage of the reported nucleotide-binding pocket (NBP) in the Fab arms of immunoglobulins by developing indole-based, 5-fluoro-2,4-dinitrobenzene-derivatized OBOC peptide libraries for the identification of affinity elements that can be used as site-specific derivatization agents against both mono- and polyclonal antibodies...
January 20, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/26364917/screening-and-identification-of-mimotopes-of-the-major-shrimp-allergen-tropomyosin-using-one-bead-one-compound-peptide-libraries
#11
Nicki Yh Leung, Christine Yy Wai, Marco Hk Ho, Ruiwu Liu, Kit S Lam, Jin Jun Wang, Shang An Shu, Ka Hou Chu, Patrick Sc Leung
The one-bead-one-compound (OBOC) combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E (IgE) epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA...
September 14, 2015: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/26290177/dna-encoded-solid-phase-synthesis-encoding-language-design-and-complex-oligomer-library-synthesis
#12
Andrew B MacConnell, Patrick J McEnaney, Valerie J Cavett, Brian M Paegel
The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation...
September 14, 2015: ACS Combinatorial Science
https://www.readbyqxmd.com/read/26252756/development-of-a-plate-based-screening-assay-to-investigate-the-substrate-specificity-of-the-prmt-family-of-enzymes
#13
Hao C Nguyen, Min Wang, Andrew Salsburg, Bryan Knuckley
There are nine protein arginine methyltransferases (PRMTs 1-9) expressed in humans that vary in both subcellular localization and substrate specificity. The variation in substrate specificity between isozymes leads to competing effects that result in either activation or repression of tumor suppressor genes. Current methods used to study substrate specificity for these enzymes utilize radioisotopic labeling of substrates, mass spectrometry analysis of complex samples, or coupled assays that monitor cofactor degradation...
September 14, 2015: ACS Combinatorial Science
https://www.readbyqxmd.com/read/26221913/optimization-of-the-magnetic-recovery-of-hits-from-one-bead-one-compound-library-screens
#14
Kimberly Mendes, J M Ndungu, Lorraine F Clark, Thomas Kodadek
On-bead screening of one-bead-one-compound (OBOC) libraries is a useful procedure for the identification of protein ligands. An important aspect of this experiment is the method by which beads that bind the target protein are separated from those that do not. Ideally, such a method would be rapid and convenient and result in the isolation of 100% of the "hits" with no false positives (beads that display compounds that are not good ligands for the target). We introduced a technique in which beads that have bound a labeled target protein can be magnetized, thus allowing their convenient isolation ( Astle et al...
September 14, 2015: ACS Combinatorial Science
https://www.readbyqxmd.com/read/26067174/high-affinity-binding-of-conformationally-constrained-synthetic-oligomers-to-an-antigen-specific-antibody-discovery-of-a-diagnostically-useful-synthetic-ligand-for-murine-type-1-diabetes-autoantibodies
#15
Todd M Doran, Yu Gao, Scott Simanski, Patrick McEnaney, Thomas Kodadek
'Antigen surrogates' are synthetic, non-natural molecules that recognize the antigen-binding sites of antibodies. These molecules are of interest as replacements for native antigens as antibody 'capture agents' in ELISA-like assays of potential diagnostic utility, for example when the antibody is indicative of a disease state. Antigen surrogates for disease-related antibodies can be mined from one-bead one-compound (OBOC) libraries by first denuding the library of ligands for antibodies present in the serum of control patients or animals, followed by screening the remainder of the library against serum from individuals with a particular disease of interest...
November 1, 2015: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26017924/direct-identification-of-on-bead-peptides-using-surface-enhanced-raman-spectroscopic-barcoding-system-for-high-throughput-bioanalysis
#16
Homan Kang, Sinyoung Jeong, Yul Koh, Myeong Geun Cha, Jin-Kyoung Yang, San Kyeong, Jaehi Kim, Seon-Yeong Kwak, Hye-Jin Chang, Hyunmi Lee, Cheolhwan Jeong, Jong-Ho Kim, Bong-Hyun Jun, Yong-Kweon Kim, Dae Hong Jeong, Yoon-Sik Lee
Recently, preparation and screening of compound libraries remain one of the most challenging tasks in drug discovery, biomarker detection, and biomolecular profiling processes. So far, several distinct encoding/decoding methods such as chemical encoding, graphical encoding, and optical encoding have been reported to identify those libraries. In this paper, a simple and efficient surface-enhanced Raman spectroscopic (SERS) barcoding method using highly sensitive SERS nanoparticles (SERS ID) is presented. The 44 kinds of SERS IDs were able to generate simple codes and could possibly generate more than one million kinds of codes by incorporating combinations of different SERS IDs...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25879633/high-throughput-sorting-and-placement-of-one-bead-one-compound-oboc-libraries-from-bulk-to-single-wells-in-organic-solvent
#17
Mark W Bordo, Rafiou Oketokoun, Conor J Cross, Kai Bao, Jeong Heon Lee, Ilya Feygin, Alex B Chang, John V Frangioni, Hak Soo Choi
One-bead-one-compound (OBOC) solid-phase combinatorial chemistry has been used extensively in drug discovery. However, a major bottleneck has been the sorting of individual beads, while still swollen in organic solvent, into individual wells of a microwell plate. To solve this problem, we have constructed an automated bead sorting system with integrated quality control that is capable of sorting and placing large numbers of beads in bulk to single wells of a 384-well plate, all in an organic solvent. The bead sorter employs a unique, reciprocating fluidic design capable of depositing 1 bead every 1...
May 11, 2015: ACS Combinatorial Science
https://www.readbyqxmd.com/read/25675215/palladium-catalyzed-asymmetric-allylation-of-3-oboc-oxindoles-an-efficient-synthesis-of-3-allyl-3-hydroxyoxindoles
#18
Samydurai Jayakumar, Nandarapu Kumarswamyreddy, Muthuraj Prakash, Venkitasamy Kesavan
3-Allyl-3-hydroxyoxindoles were synthesized in very good enantio- (up to 97% ee) and diastereoselectivities (dr up to 7.6:1) with contiguous quaternary and tertiary stereogenic centers by employing tartrate derived bi(oxazoline) in Pd-catalyzed allylation of 3-OBoc-oxindole. Synthetic utility of 3-allyl-3-hydroxyoxindole was demonstrated by synthesizing a highly substituted spiro(oxindole-3,2'-tetrahydrofuran) derivative in good yield and stereoselectivity.
March 6, 2015: Organic Letters
https://www.readbyqxmd.com/read/25618725/label-free-detection-microarray-for-novel-peptide-ligands-screening-base-on-ms-spri-combination
#19
Weizhi Wang, Di Zhang, Zewen Wei, Zihua Wang, Xiangli Bu, Shu Yang, Qiaojun Fang, Zhiyuan Hu
Peptides ligands with high affinity and high specificity towards specific targets is catching a good deal of interests in biomedical field. Traditional peptide screening procedure involves selection, sequencing and characterization and each step is time-consuming and labor-intensive. The combination between different analytical methods could provide an integrated plan for efficient peptide screening. We report herein a label-free detection microarray system to facilitate the whole one-bead-one-compound (OBOC) peptide screening process...
March 2015: Talanta
https://www.readbyqxmd.com/read/25616336/synthesis-and-cell-based-screening-of-one-bead-one-compound-peptide-libraries
#20
REVIEW
Fernanda C Bononi, Leonard G Luyt
Combinatorial one-bead-one-compound (OBOC) peptide library screening has proven to be a powerful tool for identification of small molecules, peptides, or peptidomimetics against a variety of specific targets such as cell surface receptors, protein kinases, proteases, and phosphatases. With each bead displaying many copies of a single chemical entity, millions of compounds can be rapidly synthesized and screened with whole-cell binding on-bead functional assays. Here we describe the methodology for the synthesis, screening, and sequence deconvolution of an OBOC peptide library analyzed for affinity to a cancer cell line...
2015: Methods in Molecular Biology
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