A5081725831- Monoclonal and Polyclonal Antibodies Research
- Nanoparticle-Based Drug Delivery
- Food Allergy and Anaphylaxis Research
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Allergic Rhinitis and Sensitization
- Multiple Myeloma Research and Treatments
- Mast cells and histamine
- Asthma and respiratory diseases
- Protein purification and stability
- Click Chemistry and Applications
- Lipid Membrane Structure and Behavior
- Dendrimers and Hyperbranched Polymers
- Supramolecular Self-Assembly in Materials
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Advanced Biosensing Techniques and Applications
- Drug-Induced Adverse Reactions
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Multicomponent Synthesis of Heterocycles
- Viral Infectious Diseases and Gene Expression in Insects
- Contact Dermatitis and Allergies
- Gold and Silver Nanoparticles Synthesis and Applications
- Nanoplatforms for cancer theranostics
University of Notre Dame
2014-2024
Mike and Josie Harper Cancer Research Institute
2018-2020
National Center for Genetic Engineering and Biotechnology
2015
John Wiley & Sons (United States)
2015
Bioengineering Center
2015
Advanced Cell Diagnostics (United States)
2014
Harvard University
2007-2011
Baylor University
2010
University of California, Los Angeles
2010
Tufts University
2001-2006
PEGylated liposomes are attractive pharmaceutical nanocarriers; however, literature reports of ligand-targeted nanoparticles have not consistently shown successful results. Here, we employed a multifaceted synthetic strategy to prepare peptide-targeted liposomal with high purity, reproducibility, and precisely controlled stoichiometry functionalities evaluate the role PEG coating, peptide EG-linker length, valency on cellular uptake in systematic manner. We analyzed these parameters two...
The amino acid substitution or post-translational modification of a cytosolic protein can cause unpredictable changes to its electrophoretic mobility during SDS-PAGE. This type "gel shifting" has perplexed biochemists and biologists for decades. We identify mechanism that predominates among set ALS (amyotrophic lateral sclerosis) mutant hSOD1 (superoxide dismutase) proteins, post-translationally modified homologous SOD1 proteins from different organisms. By first comparing how 39...
Cisplatin is a first line chemotherapy for most types of cancer. However, its use dose-limited due to severe nephrotoxicity. Here we report the rational engineering novel nanoplatinate inspired by mechanisms underlying cisplatin bioactivation. We engineered polymer, glucosamine-functionalized polyisobutylene-maleic acid, where platinum (Pt) can be complexed monomeric units using monocarboxylato and an O → Pt coordinate bond. show that at unique polymer ratio, this complex self-assembles into...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTProgrammed Self-Sorting of Coiled Coils with Leucine and Hexafluoroleucine CoresBasar Bilgiçer, Xuechao Xing, Krishna KumarView Author Information Department Chemistry, Tufts University Medford, Massachusetts 02155-5813 Cite this: J. Am. Chem. Soc. 2001, 123, 47, 11815–11816Publication Date (Web):November 3, 2001Publication History Received6 August 2001Published online3 November inissue 1...
The design, synthesis, and structural characterization of a highly fluorinated peptide system based on the coiled coil region yeast transcription factor GCN4 is described. All four leucine residues (a position) three valine (d were replaced by unnatural amino acids 5,5,5-trifluoroleucine 4,4,4-trifluorovaline, respectively. α-helical at low micromolar concentrations as judged circular dichroism spectra, sediments dimeric species in 5−30 μM concentration range, exhibits dimer melting...
This paper describes a synthetic dimer of carbonic anhydrase, and series bivalent sulfonamide ligands with different lengths (25 to 69 Å between the ends fully extended ligands), as model system use in examining binding antibodies antigens. Assays based on analytical ultracentrifugation fluorescence indicate that this forms cyclic, noncovalent complexes stoichiometry one ligand dimer. binds low picomolar avidities (Kdavidity = 3–40 pM). A structurally analogous monovalent active site Kdmono...
In the continuing search for effective cancer treatments, we report rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion multiple myeloma (MM) cells to bone marrow stroma confers MM cell-adhesion-mediated drug resistance (CAM-DR). our design, used micellar nanoparticles as dynamic self-assembling scaffolds present VLA-4-antagonist peptides doxorubicin...
In this study, we describe the development of liposomal bortezomib nanoparticles, which was accomplished by synthesizing prodrugs with reversible boronic ester bonds and then incorporating resulting into nanoparticles via surface conjugation. Initially, several prodrug candidates were screened based upon stability using isobutylboronic acid as a model compound. The two most stable selected to create conjugated on liposomes. Our strategy yielded narrow size range 100 nm high reproducibility....
Ligand-targeted nanoparticles are emerging drug delivery vehicles for cancer therapy. Here, we demonstrate that the cellular uptake of peptide-targeted liposomes and micelles can be significantly enhanced by increasing hydrophilicity targeting peptide sequence while simultaneously optimizing EG peptide-linker length. Two distinct disease models were analyzed, as functionalized with either VLA-4 or HER2 antagonistic peptides to target multiple myeloma breast cells, respectively. Our results...
Abstract Here, we report the synthesis and evaluation of dual drug–loaded nanoparticles as an effective means to deliver carfilzomib doxorubicin multiple myeloma tumor cells at their optimal synergistic ratio. First, various molar ratios were screened against cell lines determine ratio that elicited greatest synergy using Chou–Talalay method. The therapeutic agents then incorporated into liposomes 1:1 yield with a narrow size range 115 nm high reproducibility. Our results demonstrated...
Small dimensions of gold nanoparticles (AuNPs) necessitate antibodies to be immobilized in an oriented fashion order conserve their antigen binding activity for proper function. In this study, we used the previously described UV-NBS method site-specifically incorporate a thioctic acid (TA) functionality into at conserved nucleotide-binding site (NBS). Modified were on AuNP surface manner utilizing newly incorporated TA while maintaining antibody structure and activity. The resulting...
Dual-targeted liposomes achieve increased uptake and selectivity for multiple myeloma cells through cooperative peptide targeting of LPAM-1 VLA-4.
Control of structure and function in membrane proteins remains a formidable challenge. We report here new design paradigm for the self-assembly protein components context nonpolar environments biological membranes. An incrementally staged assembly process relying on unique properties fluorinated amino acids was used to drive transmembrane helix-helix interactions. In first step, hydrophobic peptides partitioned into micellar lipids. Subsequent phase separation simultaneously lipophobic...
This paper reports that the acetylation of lysine epsilon-NH3(+) groups alpha-amylase--one most important hydrolytic enzymes used in industry--produces highly negatively charged variants are enzymatically active, thermostable, and more resistant than wild-type enzyme to irreversible inactivation on exposure denaturing conditions (e.g., 1 h at 90 degrees C solutions containing 100-mM sodium dodecyl sulfate). Acetylation also protected against by neutral surfactant TRITON X-100 (polyethylene...
The conserved nucleotide binding site (NBS), found on the Fab variable domain of all antibody isotypes, remains a not-so-widely known and unutilized site. Here, we describe UV photo-cross-linking method (UV-NBS) that utilizes NBS for oriented immobilization antibodies onto surfaces, such antigen activity unaffected. Indole-3-butyric acid (IBA) has an affinity with K(d) ranging from 1 to 8 μM different isotypes can be covalently photo-cross-linked at upon exposure light. Using UV-NBS method,...
The conserved nucleotide binding site (NBS), found within the Fab variable domain of antibodies, remains a not-so-widely known and underutilized site. Here we describe novel affinity chromatography method that utilizes NBS as target for selectively purifying antibodies from complex mixtures. column was prepared by coupling indole butyric acid (IBA), which has monovalent with K(d) ranging between 1 8 μM, to ToyoPearl resin resulting in targeting (NBS(IBA)). proof-of-concept studies performed...
Nanoparticles formed via electrostatic interactions between methoxy-polyethylene glycol-block-poly(glutamic acid) (MPEG-PGA) and a multinuclear platinum(II) drug, di-cisPt, exhibit efficient platinum loading, improved cellular uptake, in vitro cytotoxicity, enhanced vivo efficacy.
Abstract Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show signaling is associated with poor outcomes patients various forms of lung cancer, and required for growth multiple mouse models. CD4 + T cell-derived promotes the expansion both CD11c − interstitial macrophage populations Mechanistically, IL-9/macrophage axis requires arginase 1 (Arg1) to mediate Indeed, Arg1 but not - macrophages Il9r...