Relevant bibliographies by topics / Multivalent therapeutics

Academic literature on the topic 'Multivalent therapeutics'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Contents

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Multivalent therapeutics.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "Multivalent therapeutics"

1

Farhadi, Shaheen A., and Gregory A. Hudalla. "Engineering galectin–glycan interactions for immunotherapy and immunomodulation." Experimental Biology and Medicine 241, no. 10 (May 2016): 1074–83. http://dx.doi.org/10.1177/1535370216650055.

Full text
Abstract:
Galectins, a 15-member family of soluble carbohydrate-binding proteins, are receiving increasing interest as therapeutic targets for immunotherapy and immunomodulation due to their role as extracellular signals that regulate innate and adaptive immune cell phenotype and function. However, different galectins can have redundant, synergistic, or antagonistic signaling activity in normal immunological responses, such as resolution of inflammation and induction of antigen-specific tolerance. In addition, certain galectins can be hijacked to promote progression of immunopathologies, such as tumor immune privilege, metastasis, and viral infection, while others can inhibit these processes. Thus, eliciting a desired immunological outcome will likely necessitate therapeutics that can precisely enhance or inhibit particular galectin–glycan interactions. Multivalency is an important determinant of the affinity and specificity of natural galectin–glycan interactions, and is emerging as a key design element for therapeutics that can effectively manipulate galectin bioactivity. This minireview surveys current molecular and biomaterial engineering approaches to create therapeutics that can stabilize galectin multivalency or recapitulate natural glycan multivalency (i.e. “the glycocluster effect”). In particular, we highlight examples of using natural and engineered multivalent galectins for immunosuppression and immune tolerance, with a particular emphasis on treating autoimmune diseases or avoiding transplant rejection. In addition, we present examples of multivalent inhibitors of galectin–glycan interactions to maintain or restore T-cell function, with a particular emphasis on promoting antitumor immunity. Finally, we discuss emerging opportunities to further engineer galectin–glycan interactions for immunotherapy and immunomodulation.
APA, Harvard, Vancouver, ISO, and other styles
2

Lee, JuYeon, Yugang Bai, Ullas V. Chembazhi, Shaohong Peng, Kevin Yum, Long M. Luu, Lauren D. Hagler, et al. "Intrinsically cell-penetrating multivalent and multitargeting ligands for myotonic dystrophy type 1." Proceedings of the National Academy of Sciences 116, no. 18 (April 11, 2019): 8709–14. http://dx.doi.org/10.1073/pnas.1820827116.

Full text
Abstract:
Developing highly active, multivalent ligands as therapeutic agents is challenging because of delivery issues, limited cell permeability, and toxicity. Here, we report intrinsically cell-penetrating multivalent ligands that target the trinucleotide repeat DNA and RNA in myotonic dystrophy type 1 (DM1), interrupting the disease progression in two ways. The oligomeric ligands are designed based on the repetitive structure of the target with recognition moieties alternating with bisamidinium groove binders to provide an amphiphilic and polycationic structure, mimicking cell-penetrating peptides. Multiple biological studies suggested the success of our multivalency strategy. The designed oligomers maintained cell permeability and exhibited no apparent toxicity both in cells and in mice at working concentrations. Furthermore, the oligomers showed important activities in DM1 cells and in a DM1 liver mouse model, reducing or eliminating prominent DM1 features. Phenotypic recovery of the climbing defect in adult DM1Drosophilawas also observed. This design strategy should be applicable to other repeat expansion diseases and more generally to DNA/RNA-targeted therapeutics.
APA, Harvard, Vancouver, ISO, and other styles
3

Force Aldred, Shelley, Andrew Boudreau, Ben Buelow, Starlynn Clarke, Kevin Dang, Laura Davison, Katherine Harris, et al. "Multispecific antibodies targeting CD38 show potent tumor-specific cytotoxicity." Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 57. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.57.

Full text
Abstract:
57 Background: Multivalent antibodies targeting either CD38 alone or CD38 in conjunction with PD-L1 may yield therapeutics with superior biological activities and provide benefit for treating malignancies expressing low levels of CD38 (MCL, NHL, T cell lymphomas and Daratumumab refractory MM). Multivalent, multispecific antibodies kill CD38low cells through a variety of mechanisms including stronger and more specific engagement of CD38. Potent and directed immune checkpoint inhibition is realized by adding an anti-PD-L1 binding domain. Teneobio’s discovery platform utilizes VH domains (UniDabs) of fully human heavy chain antibodies (UniAbs) to develop bi-, tri-, and tetravalent antibodies. Methods: Individual UniDabs targeting CD38 and PDL1 were identified using our unique sequence-based discovery platform and high-throughput lead evaluation pipeline (TeneoSeek). This robust screening workflow enables evaluation of a large diversity of natural fully human antibodies, targeting multiple epitopes on a single antigen and uncovering important sequence activity relationships. UniDabs from transgenic rats are ideal building blocks for the generation of potent and highly manufacturable multivalent antibody therapeutics. Results: We have identified UniDabs that efficiently block PD-1/PD-L1 interaction as well as additional UniDabs that bind to five different functional epitopes on human CD38. Using different combinations and arrangements of UniDabs, a variety of multivalent antibodies were constructed and evaluated in in vitro models. Specific combinations of UniDabs show more potent cytotoxic effects than Daratumumab for multiple mechanisms including CDC and direct apoptosis. Conclusions: Data from a range of assay types show that multivalent UniAbs targeting CD38 can be engineered to display superior tumor cell cytotoxicity through multiple mechanisms of action.
APA, Harvard, Vancouver, ISO, and other styles
4

Chittasupho, Chuda, Teruna J. Siahaan, Charlotte M. Vines, and Cory Berkland. "Autoimmune therapies targeting costimulation and emerging trends in multivalent therapeutics." Therapeutic Delivery 2, no. 7 (July 2011): 873–89. http://dx.doi.org/10.4155/tde.11.60.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Liu, S. P., L. Zhou, R. Lakshminarayanan, and R. W. Beuerman. "Multivalent Antimicrobial Peptides as Therapeutics: Design Principles and Structural Diversities." International Journal of Peptide Research and Therapeutics 16, no. 3 (August 26, 2010): 199–213. http://dx.doi.org/10.1007/s10989-010-9230-z.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Rossi, Edmund A., David M. Goldenberg, Thomas M. Cardillo, Rhona Stein, Yang Wang, and Chien-Hsing Chang. "Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics." Cancer Research 68, no. 20 (October 15, 2008): 8384–92. http://dx.doi.org/10.1158/0008-5472.can-08-2033.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Toretsky, Jeffrey A., and Peter E. Wright. "Assemblages: Functional units formed by cellular phase separation." Journal of Cell Biology 206, no. 5 (September 1, 2014): 579–88. http://dx.doi.org/10.1083/jcb.201404124.

Full text
Abstract:
The partitioning of intracellular space beyond membrane-bound organelles can be achieved with collections of proteins that are multivalent or contain low-complexity, intrinsically disordered regions. These proteins can undergo a physical phase change to form functional granules or other entities within the cytoplasm or nucleoplasm that collectively we term “assemblage.” Intrinsically disordered proteins (IDPs) play an important role in forming a subset of cellular assemblages by promoting phase separation. Recent work points to an involvement of assemblages in disease states, indicating that intrinsic disorder and phase transitions should be considered in the development of therapeutics.
APA, Harvard, Vancouver, ISO, and other styles
8

Blanchard, Helen, Khuchtumur Bum-Erdene, and Matthew W. Hugo. "Inhibitors of Galectins and Implications for Structure-Based Design of Galectin-Specific Therapeutics." Australian Journal of Chemistry 67, no. 12 (2014): 1763. http://dx.doi.org/10.1071/ch14362.

Full text
Abstract:
Galectins are a family of galactoside-specific lectins that are involved in a myriad of metabolic and disease processes. Due to roles in cancer and inflammatory and heart diseases, galectins are attractive targets for drug development. Over the last two decades, various strategies have been used to inhibit galectins, including polysaccharide-based therapeutics, multivalent display of saccharides, peptides, peptidomimetics, and saccharide-modifications. Primarily due to galectin carbohydrate binding sites having high sequence identities, the design and development of selective inhibitors targeting particular galectins, thereby addressing specific disease states, is challenging. Furthermore, the use of different inhibition assays by research groups has hindered systematic assessment of the relative selectivity and affinity of inhibitors. This review summarises the status of current inhibitors, strategies, and novel scaffolds that exploit subtle differences in galectin structures that, in conjunction with increasing available data on multiple galectins, is enabling the feasible design of effective and specific inhibitors of galectins.
APA, Harvard, Vancouver, ISO, and other styles
9

Miyashita, Shin-Ichiro, Jie Zhang, Sicai Zhang, Charles B. Shoemaker, and Min Dong. "Delivery of single-domain antibodies into neurons using a chimeric toxin–based platform is therapeutic in mouse models of botulism." Science Translational Medicine 13, no. 575 (January 6, 2021): eaaz4197. http://dx.doi.org/10.1126/scitranslmed.aaz4197.

Full text
Abstract:
Efficient penetration of cell membranes and specific targeting of a cell type represent major challenges for developing therapeutics toward intracellular targets. One example facing these hurdles is to develop post-exposure treatment for botulinum neurotoxins (BoNTs), a group of bacterial toxins (BoNT/A to BoNT/G) that are major potential bioterrorism agents. BoNTs enter motor neurons, block neurotransmitter release, and cause a paralytic disease botulism. Members of BoNTs such as BoNT/A exhibit extremely long half-life within neurons, resulting in persistent paralysis for months, yet there are no therapeutics that can inhibit BoNTs once they enter neurons. Here, we developed a chimeric toxin–based delivery platform by fusing the receptor-binding domain of a BoNT, which targets neurons, with the membrane translocation domain and inactivated protease domain of the recently discovered BoNT-like toxin BoNT/X, which can deliver cargoes across endosomal membranes into the cytosol. A therapeutic protein was then created by fusing a single-domain antibody (nanobody) against BoNT/A with the delivery platform. In vitro characterization demonstrated that nanobodies were delivered into cultured neurons and neutralized BoNT/A in neurons. Administration of this protein in mice shortened duration of local muscle paralysis, restoring muscle function within hours, and rescued mice from systemic toxicity of lethal doses of BoNT/A. Fusion of two nanobodies, one against BoNT/A and the other against BoNT/B, created a multivalent therapeutic protein able to neutralize both BoNT/A and BoNT/B in mice. These studies provide an effective post-exposure treatment for botulism and establish a platform for intracellular delivery of therapeutics targeting cytosolic proteins and processes.
APA, Harvard, Vancouver, ISO, and other styles
10

Heitner, Tara, Noboru Satozawa, Kirk Mclean, David Vogel, Ronald R. Cobb, Bing Liu, Mithra Mahmoudi, et al. "Obligate Multivalent Recognition of Cell Surface Tomoregulin following Selection from a Multivalent Phage Antibody Library." Journal of Biomolecular Screening 11, no. 8 (December 2006): 985–95. http://dx.doi.org/10.1177/1087057106293841.

Full text
Abstract:
A therapeutic antibody candidate (AT-19) isolated using multivalent phage display binds native tomoregulin (TR) as a mul-timer not as a monomer. This report raises the importance of screening and selecting phage antibodies on native antigen and reemphasizes the possibility that potentially valuable antibodies are discarded when a monomeric phage display system is used for screening. A detailed live cell panning selection and screening method to isolate multivalently active antibodies is described. AT-19 is a fully human antibody recognizing the cell surface protein TR, a proposed prostate cancer target for therapeutic antibody internalization. AT-19 was isolated from a multivalent single-chain variable fragment (scFv) antibody library rescued with hyperphage. The required multivalency for isolation of AT-19 is supported by fluorescence activated cell sorting data demonstrating binding of the multivalent AT-19 phage particles at high phage concentrations and failure of monovalent particles to bind. Pure monomeric scFv AT-19 does not bind native receptor on cells, whereas dimeric scFv or immunoglobulin G binds with nanomolar affinity. The isolation of AT-19 antibody with obligate bivalent binding activity to native TR is attributed to the use of a multivalent display of scFv on phage and the method for selecting and screening by alternate use of 2 recombinant cell lines.
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "Multivalent therapeutics"

1

Alias, Nadiawati. "Multivalent sialic acid binding proteins as novel therapeutics for influenza and parainfluenza infection." Thesis, University of St Andrews, 2014. http://hdl.handle.net/10023/4479.

Full text
Abstract:
In nature, proteins with weak binding affinity often use a multivalency approach to enhance protein affinity via an avidity effect. Interested in this multivalency approach, we have isolated a carbohydrate binding module (CBM) that recognises sialic acid (known as a CBM40 domain) from both Vibrio cholerae (Vc) and Streptococcus pneumoniae (Sp) NanA sialidases, and generated multivalent polypeptides from them using molecular biology. Multivalent CBM40 constructs were designed either using a tandem repeat approach to produce trimeric or tetrameric forms that we call Vc3CBM and Vc4CBM, respectively, or through the addition of a trimerization domain derived from Pseudomonas aeruginosa pseudaminidase to produce three trimeric forms of proteins known as Vc-CBMTD (WT), Vc-CBMTD (Mutant) and Sp-CBMTD). Due to the position and flexibility of the linker between the trimerization domain and the CBM40 domain, site directed mutagenesis was employed to introduce a disulphide bond between the monomers at positions S164C and T83C of the CBM40 domain in order to promote a stable orientation of the binding site for easier access of sialic acids. Data from isothermal titration calorimetry (ITC) reveals that interaction of multivalent CBM40 proteins with α(2,3)-sialyllactose was mainly enthalpy driven with entropy contributing unfavorably to the interaction suggesting that these proteins establish a strong binding affinity to their ligand minimizing dissociation to produce stable multivalent molecules. However, using surface plasmon resonance (SPR), a mixed balance of entropy and enthalpy contributions was found with all constructs as determined by Van't Hoff plots. This proved that binding does not occur through a simple protein-ligand interaction but through disruption of hydrophobic and/or ionic hydration that provide the driving force to the process. Interestingly, the valency of multiple-linked polypeptides also plays an important part in the protein stabilization. However, little is known about their detailed structure when in multivalent form, as attempts to crystallize the whole protein molecule of Vc-CBMTD (WT) failed due to linker and domain flexibility. Only the trimerization domain (TD) part from Pseudomonas aeruginosa pseudaminidase was successfully crystallized and structure was determined to 3.0 Å without its CBM40 domain attached. In this thesis, we have also reported on the potential anti-influenza and anti- parainfluenza properties of these proteins, which were found to block attachment and inhibit infection of several influenza A and parainfluenza virus strains in vitro. As widely mentioned in literature, terminal sialic acids on the cell surface of mammalian host tissue provide a target for various pathogenic organisms to bind. Levels of viral inhibition were greatest against A/Udorn/72 H3N2 virus for Vc4CBM and Vc3CBM constructs with the lowest EC50 of 0.59 µM and 0.94 µM respectively, however most of the multivalent proteins tested were also effective against A/WSN/33 H1N1 and A/PR8/34 H1N1 subtypes. For parainfluenza virus, all constructs containing V. cholerae sialidase CBM40 domain showed great effect in inhibiting virus infection during cell protection assay. The best EC50 values were 0.2 µM from Vc-CBMTD (WT) followed by 1.17 µM from Vc4CBM and 1.78 µM from Vc-CBMTD (Mutant) which was against hPIV2, hPIV3 and hPIV5 infections respectively. Only a construct from S. pneumoniae sialidase known as Sp-CBMTD showed negligible effect on cell protection. All constructs were further tested for cytotoxicity in mammalian cell culture as well as undergoing an inhibition study on viral replication proteins. For the in vivo study, we also demonstrated the effectiveness of Vc4CBM to protect cotton rats and mice from hPIV3 and Streptococcus pneumoniae infections, when given intranasally in advance or on the day of infection. Therefore, these novel multivalent proteins could be promising candidates as broad-spectrum inhibitors or as a prophylactic treatment for both influenza and parainfluenza associated diseases.
APA, Harvard, Vancouver, ISO, and other styles
2

Holliger, Philipp. "Multivalent and bispecific antibody fragments from E.coli : new strategies for antibody-based diagnostics and therapeutics from bacteria /." [S.l.] : [s.n.], 1994. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=11012.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Hart, Nathaniel. "Combinatorial Targeting of the Glucagon-Like Peptide-1 And Sulfonylurea-1 Receptors Using a Complimentary Multivalent Glucagon-Like Peptide-1/Glibenclamide Ligand for the Improvement of β-Cell Targeting Agents and Diabetic Treatment." Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/311363.

Full text
Abstract:
A scourge of Type I and Type II diabetes impacts the health of hundreds of millions worldwide. The number and prevalence of diabetics are expected to rise dramatically in the next two decades. Diabetes is defined by chronic hyperglycemia which can result in a number of detrimental and costly metabolic, renal, cardiovascular and neurological disorders. Identification of at risk individuals and effective blood glucose management are critical to improving diabetic outcomes and preventing hyperglycemic complications. Diabetes prevention and treatment is limited by the understanding of islet function and mass in the diabetogenic and diabetic state. The islets of Langerhans are dispersed throughout the pancreas and comprise <2% of the pancreatic mass. The reclusive nature of islet cells presents unique challenges understanding disease development. No agent capable of exclusively targeting pancreatic β-cells within the islet has been discovered and the lack of targeting agent specificity impedes efforts to: quantify β-cell mass and develop novel therapeutics. We propose β-cell targeting can be improved by targeting unique combinations of receptors simultaneously with multivalent ligands. A synthetic multivalent agent composed of two β-cell specific diabetic therapeutics, glucagon-like peptide-1 (GLP-1) and glibenclamide (Glb), targeted against the GLP-1R and the sulfonylurea-1 receptor (SUR1) is a lead compound for the development of specific bi-functional islet cell targeting agents for use in the in vivo detection and treatment of β -cells. Herein, we describe the synthesis and initial characterization of a heterobivalent ligand composed of GLP-1 coupled to Glb. The heterobivalent ligand binds to an unaltered β-cell line with increased specificity relative to a human pancreatic exocrine cell line. Additionally, receptor cross-linking modifies β-cell signaling. Exposure of β-cells to the heterobivalent ligand results in antagonism of SUR1-Ca²⁺ signaling and equipotent agonism of GLP-1R-cAMP signaling, in comparison to the cognate monomeric ligands (Glb and GLP-1). Perturbations in intracellular signaling modifies β-cell insulin secretion resulting in decreased basal insulin secretion and with maintained yet reduced ability to potentiate β-cell glucose stimulated insulin secretion. GLP-1/Glb β-cell specificity and functional modulation suggests combinatorial receptor targeting is an effective strategy for the development of bi-functional cell-specific targeting agents, warranting further investigation and optimization.
APA, Harvard, Vancouver, ISO, and other styles
4

Ananthakrishnan, Kameswari, and Kameswari Ananthakrishnan. "Improved β-Cell Targeting and Therapeutics Using Multivalent Glucagon-Like Peptide-1 (GLP-1) Linked to the α2AR Antagonist Yohimbine (YHB): Evaluating the Binding, Selectivity and Signaling." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/623004.

Full text
Abstract:
Diabetes Mellitus (DM) is a metabolic disorder in which the body fails to achieve glucose homeostasis, due to either insulin resistance or reduced insulin secretion or both. This inadequate glucose control leads to hyperglycemia which, if left unchecked, leads to secondary complications like nephropathy, neuropathy, retinal degeneration and other serious conditions. In non-disease state, normal glucose level in the blood is maintained by pancreatic β-cells, which secrete insulin. However, during diabetes development, there is loss of β-cell mass and function; resulting in decreased insulin secretion which is the ultimate cause of hyperglycemia. The ability to non-invasively monitor changes in the β-cell mass during the development or treatment of diabetes would be a significant advance in diabetes management. However, a primary limitation for analysis of β-cell mass and developing dysfunction is the lack of specificity of β-cell targeting agents. Our novel approach for achieving the required specificity for a usable β-cell targeted contrast agent is to target a set of receptors on the cell surface that, as a combination, are unique to that cell. Through genetic screening, Glucagon Like Peptide-1 Receptor (GLP-1R) and α2Adrenergic Receptor (α2AR) were chosen as a potential molecular barcode for β-cells since their combination expression is relatively unique to the β-cells. GLP-1R and α2AR are both G-protein couple receptors (GPCRs) that, apart from being a β-cell specific combination, play an important role in regulating fundamental downstream signaling pathways in β-cells. To target these receptors effectively, we synthesized a multivalent ligand composed of Yohimbine (Yhb), an α2 adrenergic receptor (α2AR) antagonist, linked to an active Glucagon-like Peptide 1 analog (GLP-1₇₋₃₆). In this manuscript, I describe the synthesis and characterization of binding selectivity and signaling ability of GLP-1/Yhb at the cellular level. Using high throughput binding assays, we observed high affinity binding of GLP-1/Yhb to βTC3 cells, a β-cell mimetic line expressing both receptors, at a Kd of ~3 nM. Using microscopy, we observed significant Cy5-tagged GLP-1/Yhb binding and rapid internalization in cells expressing the complementary receptor pair at low concentrations, as low as 1 nM and 5 nM. When one of the receptors was made inaccessible due to presence of saturating quantities of a single unlabeled monomer, GLP-1/Yhb-Cy5 failed to bind to the cells at low concentrations (<10 nM). Similarly, in cells where either GLP-1R or α2AR were knocked down (using shRNA), binding of GLP-1/Yhb was significantly reduced (≤half of cells with both receptors), indicating strong selectivity of the ligand to cells expressing the combination of receptors. We also observed that GLP-1/Yhb construct modulates downstream signaling inβ TC3 cells resulting in enhanced Glucose Stimulated Insulin Secretion (GSIS). In presence of stimulatory glucose, GLP-1/Yhb significantly potentiated GSIS with a half-maximal effective dose of 2.6 nM. Compared to GLP-1₇₋₃₆ alone or GLP-1₇₋₃₆ and Yhb monomers added together, only GLP-1/Yhb could significantly potentiate GSIS at 1 nM, demonstrating that GLP-1/Yhb could translate high affinity binding to increased efficacy for GSIS potentiation. Unlike for insulin secretion, high affinity divalent binding did not translate to increased cAMP production at low concentrations, with significant increases above baseline seen only at 10 nM and higher. Nevertheless, these data show that GLP-1/Yhb binds selectively to β-cells and affects signaling, demonstrating its potential for targeted β-cell imaging and therapy. Overall, our work indicates that synthetic heterobivalent ligands, such as GLP-1/Yhb can be developed to increase cellular specificity and sensitivity making them a strong candidate for both noninvasive imaging and targeted therapy.
APA, Harvard, Vancouver, ISO, and other styles
5

Reimann, Sabine [Verfasser]. "Multivalent Dendritic Polyglycerol Anions for Diagnostic and Therapeutic Applications / Sabine Reimann." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1137206640/34.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Seifert, Oliver [Verfasser], and Roland [Akademischer Betreuer] Kontermann. "TRAIL-based multivalent and multifunctional fusion proteins and liposomes for therapeutic applications / Oliver Seifert. Betreuer: Roland Kontermann." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2014. http://d-nb.info/1056910585/34.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Josan, Jatinder Singh. "Heteromultivalent Ligands Directed Targeting of Cell-Surface Receptors - Implications in Cancer Diagnostics and Therapeutics." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/193592.

Full text
Abstract:
Effective detection and treatment of tumor malignancies depends upon identifying targets – molecular markers that differentiate cancer cells from healthy cells. Current cancer therapies involve targeting overexpressed specific gene products. An alternative approach is proposed here: to specifically target combinations of cell-surface receptors using heteromultivalent ligands (htMVLs). There are about 2500 genes encoding for cellsurface proteins in the human genome that can potentially be targeted. Taken as sets, there can be ~ 10⁶ two-receptor combinations and ~ 10⁹ three-receptor combinations available. Our group envisions that using cell-surface protein combinations that are expressed on a cancer cell but not on a normal cell, multivalent constructs displaying complementary ligands of weak affinities can be assembled. These multivalent ligands should bind with high avidity to cancer populations in vivo, and provide a degree of specificity not seen with current approaches. As a proof-of-concept, a series of multivalent ligands were designed and synthesized for a model system consisting of the human Melanocortin subtype 4 receptor (hMC4R) and the Cholecystokinin subtype 2 receptor (CCK-2R). Modeling studies on GPCR dimers predicted that a minimum linker span of 20 - 50 Å would be required to non-covalently crosslink these two receptors. The multivalent ligands were assembled using a modular parallel synthesis approach and using solidphase chemistries. A variety of linkers were explored ranging from highly rigid to highly flexible, and using natural and/or synthetic building blocks. Ligand binding affinities were evaluated using a lanthanide based competitive binding assay in cells that expressed both receptors (bivalent binding) vs those that expressed only one of the receptors (monovalent binding), and were demonstrated to have enhanced binding affinities of up to nearly two orders of magnitude. The promising ligands were further explored by synthesizing fluorescently labeled and/or lanthanide chelate labeled monovalent and heterobivalent ligands designed for in vitro and in vivo studies. More explorative work using these labeled constructs is in progress. To the best of our knowledge, the author believes this is the first such demonstration of a 'synthetic htMVL' directed recruitment and crosslinking of two heterologous cell-surface receptors. This receptor combination approach opens up new possibilities for single cell imaging, cancer detection and therapeutic intervention, and can provide a revolutionary new platform technology with which to direct therapeutics to defined cell populations.
APA, Harvard, Vancouver, ISO, and other styles
8

"Application of Multivalent Interactions for Recognition Imaging and Delivery of Therapeutics." Doctoral diss., 2016. http://hdl.handle.net/2286/R.I.39432.

Full text
Abstract:
abstract: Multivalency is an important phenomenon that guides numerous biological interactions. It has been utilized in design of therapeutics and drug candidates. Hence, this study attempts to develop analytical tools to study multivalent interactions and design multivalent ligands for drug delivery and therapeutic applications. Atomic Force Microscopy (AFM) has been envisioned as a means of nanodiagnostics due to its single molecule sensitivity. However, the AFM based recognition imaging lacks a multiplex capacity to detect multiple analytes in a single test. Also there is no user friendly wet chemistry to functionalize AFM tips. Hence, an uncatalyzed Click Chemistry protocol was developed to functionalize AFM tips. For multiplexed recognition imaging, recognition heads based on a C3 symmetrical three arm linker with azide functionalities at its ends were synthesized and the chemistry to attach them to AFM tips was developed, and these recognition heads were used in detecting multiple proteins simultaneously using AFM. A bis-Angiopeptide-2 conjugate with this three-arm linker was synthesized and this was conjugated with anti-West Nile virus antibody E16 site specifically to target advanced West Nile virus infection in the Central Nervous System. The bis-Angiopeptide-2 conjugate of the antibody shows higher efficacy compared to a linear linker-Angiopeptide-2 conjugate of the antibody in in vitro studies and currently the efficacy of this antibody conjugate in studied in mice. Surface Plasmon Resonance imaging (SPRi) results indicate that the conjugation does not affect the antigen binding activity of the antibody very significantly. A Y-shaped bisbiotin ligand was also prepared as a small sized antibody mimic. Compared to a monovalent biotin ligand, the y-Bisbiotin can cooperatively form a significantly more stable complex with streptavidin through intramolecular bivalent interactions, which were demonstrated by gel electrophoresis, SPR and AFM. Continuing on these lines, a four-arm linker was synthesized containing three single chain variable fragments (scFv) linked to the scaffold to form a tripod base, which would allow them to concomitantly interact with a trimeric Glycoprotein (GP) spike that has a “chalice” configuration. Meanwhile, a human IgG1 Fc is to be installed on the top of the tetrahedron, exerting effector functions of a monoclonal antibody.
Dissertation/Thesis
Doctoral Dissertation Chemistry 2016
APA, Harvard, Vancouver, ISO, and other styles
9

Yen-JangHuang and 黃彥彰. "Multivalent structure of nanogold-galectin-1 complex regulates apoptosis signaling and therapeutic effects in collagen-induced arthritis." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/16305030326752905343.

Full text
Abstract:
博士
國立成功大學
基礎醫學研究所
100
Cellular behaviour is controlled by numerous processes, including intracellular signaling pathways that are triggered by the binding of ligands with cell surface receptors. Multivalent ligands have multiple copies of a recognition element that binds to receptors and influences downstream signals. Gold nanoparticles are now highly utilized in chemistry, biology, engineering, and medicine. Gold nanoparticle-ligand complexes form multivalent structures to crosslink receptors with high avidity and specificity. Galectin-1 has high affinity for β-galactosides and engages with cell surface receptor to deliver a variety of intracellular signals. Galectin-1 induces apoptosis of specific thymocyte subsets and activates T cells. Here, we developed nanogold-galectin-1 (Au-Gal1) complexes with multivalent structure and expect the multivalent property of Au-Gal1 complexes will have more therapeutic potential than free-form galectin-1 or nanogold for rheumatoid arthritis. After conjugation onto gold nanoparticles, galectin-1 (Au-Gal1) bound with higher affinity to Jurkat cells to promote CD45 clustering and inhibition of its phosphatase activity, resulting in enhancement of apoptosis via caspase-dependent pathways. Au-Gal1 injected intra-articularly into rats with collagen induced arthritis (CIA) promoted apoptosis of CD4+ T cells and reduced pro-inflammatory cytokine levels in the ankle joints as well as ameliorated clinical symptoms of arthritis. These observed therapeutic effects indicate that the multivalent structure of nanoparticle-ligands can regulate the distribution of cell surface receptors and subsequent intracellular signalling, and this may provide new insights into nanoparticle applications.
APA, Harvard, Vancouver, ISO, and other styles

Book chapters on the topic "Multivalent therapeutics"

1

Sharma, Shubh D., Victor J. Hruby, Mac E. Hadley, Michael E. Granberry, and Stanley P. L. Leong. "Multivalent ligands for diagnosis and therapeutics." In Peptides, 599–600. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_236.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Liu, Cassie J., and Jennifer R. Cochran. "Engineering Multivalent and Multispecific Protein Therapeutics." In Engineering in Translational Medicine, 365–96. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-4372-7_14.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Reina, Jose J., and Javier Rojo. "Carbohydrate Multivalent Systems: Synthesis and Therapeutic Opportunities." In Carbohydrate Chemistry: State of the Art and Challenges for Drug Development, 419–39. IMPERIAL COLLEGE PRESS, 2015. http://dx.doi.org/10.1142/9781783267200_0017.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "Multivalent therapeutics"

1

Brier, Livia W., Mavish Mahomed, Amy A. Twite, Adam Barnebey, and Wesley M. Jackson. "Abstract P027: Extending intratumoral therapeutic durability using a multivalent immunotherapy platform." In Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; October 5-6, 2021. American Association for Cancer Research, 2022. http://dx.doi.org/10.1158/2326-6074.tumimm21-p027.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Liu, Yaling, Jifu Tan, and Samar Shah. "A Hybrid Model for Nanoparticle Targeted Delivery in Blood Flow." In ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology. ASMEDC, 2010. http://dx.doi.org/10.1115/nemb2010-13253.

Full text
Abstract:
Nanoparticle targeted delivery in vascular system involves the interplay of transport, hydrodynamic force, and multivalent interactions with targeted biosurfaces. Current theoretical studies in nanoparticle therapeutic delivery are limited to nanoparticle suspensions in a Newtonian fluid without blood cells [1–3]. However, blood is a complex biological fluid made of components such as red blood cells (RBC), monocytes, platelets, proteins, etc. The existence of blood cells in the core region of blood streams might change the nanoparticle dispersion and binding through cell-nanoparticle interaction. It is thus important to understand how blood cells influence nanoparticles motion and binding.
APA, Harvard, Vancouver, ISO, and other styles
3

Lapitsky, Yakov, Sabrina Alam, Udaka de Silva, Jennifer Brown, Carolina Mather, and Youngwoo Seo. "Surfactant-loaded Polyelectrolyte/multivalent Ion Coacervates for the Multi-month Release of Antibacterial and Therapeutic Payloads." In Virtual 2021 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2021. http://dx.doi.org/10.21748/am21.267.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Devi, Sarangthem V., Yun Jae Kim, Young-Jin Lee, Kuen Hur, Byung-Heon Lee, and Rang Woon Park. "Abstract 4538: Multivalent targeting based delivery of therapeutic peptide using AP1-ELP carrier for effective cancer therapy." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-4538.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Laust, Amanda K., Mikayel Mkrtichyan, Hayk Davtyan, Jivan Khlgatyan, Anahit Ghochikyan, Han Liu, Michael G. Agadjanyan, and Edward L. Nelson. "Abstract 4766: Multivalent VRP-based anti-tumor immunotherapy is an effective therapeutic strategy in a rat model of breast cancer." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-4766.

Full text
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'Multivalent therapeutics' for particular source types:
Journal articles
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography