A5031977487- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Mass Spectrometry Techniques and Applications
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Prostate Cancer Treatment and Research
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Cancer Research and Treatments
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- X-ray Diffraction in Crystallography
- Multiple Myeloma Research and Treatments
- Advanced Battery Technologies Research
- Cancer Immunotherapy and Biomarkers
- Hemoglobin structure and function
- Phenothiazines and Benzothiazines Synthesis and Activities
- Toxin Mechanisms and Immunotoxins
- Cancer-related Molecular Pathways
- Crystallization and Solubility Studies
- Electric and Hybrid Vehicle Technologies
- Synthesis and Catalytic Reactions
- Metal-Catalyzed Oxygenation Mechanisms
- Biochemical and Structural Characterization
Novartis (United States)
2022-2025
Aptevo Therapeutics (United states)
2017
Emergent BioSolutions (United States)
2013-2016
Genentech
2014
Ford Motor Company (France)
2014
Université de Montréal
2005-2010
Alexion Pharmaceuticals (United States)
2009
3M (United States)
2009
Scripps Research Institute
1998-2007
Ford Motor Company (United States)
2001
A family of anti-apoptotic regulators known as IAP (inhibitor apoptosis) proteins interact with multiple cellular partners and inhibit apoptosis induced by a variety stimuli. c-IAP (cellular IAP) 1 2 are recruited to TNFR1 (tumour necrosis factor receptor 1)-associated signalling complexes, where they mediate receptor-induced NF-kappaB (nuclear kappaB) activation. Additionally, through their E3 ubiquitin ligase activities, c-IAP1 c-IAP2 promote proteasomal degradation NIK (NF-kappaB-inducing...
Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains a highly unmet medical need and current therapies ultimately result in disease progression. Immunotherapy is rapidly growing approach for treatment but has shown limited success to date the mCRPC. We have developed novel humanized bispecific antibody, MOR209/ES414, built on ADAPTIR (modular protein technology) platform, redirect T-cell cytotoxicity toward cells by specifically targeting T through CD3ε expressing...
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting the degradation of hepatic LDL receptors (LDLRs). Current therapeutic approaches use antibodies that disrupt PCSK9 binding to LDLR reduce circulating LDL-C concentrations or siRNA reduces synthesis and thereby in circulation. Recent reports describe small molecules that, like antibodies, interfere with LDLR. We report an alternative approach decrease...
The design of a series functionally active models for manganese peroxidase (MnP) is described. Artificial metal binding sites were created near the heme cytochrome c (CCP) such that one propionates could serve as ligand. At least two these designs, MP6.1 and MP6.8, bind Mn2+ with Kd ≅ 0.2 mM, react H2O2 to form stable ferryl species, catalyze steady-state oxidation at enhanced rates relative WT CCP. kinetic parameters this activity vary considerably in presence various dicarboxylic acid...
Proteins adopt complex folds in nature that typically avoid conformations are knotted or "threaded" through closed loops. Is this the result of fundamental barriers to folding, have proteins simply evolved threaded conformations? Organic synthesis has been used supramolecular chemistry install topological links small molecules. By following these principles, we now show it is possible assemble a topologically linked protein by threading linear cyclic form [2]pseudo-rotaxane. Subsequent ring...
Backbone amide hydrogen bonds play a central role in protein secondary and tertiary structure. Previous studies have shown that substitution of backbone ester (−COO−) place (−CONH−) can selectively destabilize while maintaining similar conformation to the native The majority these focused on substitutions were accessible solvent. GCN4 coiled coil domain is an example stable α-helical dimer possesses well-packed hydrophobic core. Amino acids d positions helix, which pack core, replaced with...
Replacement of the axial histidine ligand with exogenous imidazole has been accomplished in a number heme protein mutants, where it often serves to complement functional properties protein. In this paper, we describe effects pH and buffer ion on crystal structure H175G mutant cytochrome c peroxidase, which tether between backbone is replaced by bound imidazole. The structures show that can occupy proximal cavity under experimental conditions, but details interaction coordination are markedly...
Background: B-cell maturation antigen (BCMA) is a member of the tumor necrosis factor receptor superfamily with selective expression on benign and malignant plasma cells. Signaling through BCMA mediates survival proliferation multiple myeloma (MM) validated clinical target BCMA-directed therapies approved or in development for patients relapsed and/or refractory (r/r) MM. Bispecific antibodies (BsAbs) offer convenient alternative to chimeric receptor–modified T-cell (CAR-T) targeting are...
Cyclic sulfamidates have served as reactive electrophiles for the synthesis of various products, including alkaloids, substituted amines, amino acids and lactams.N-Acyl dioxathiazinanes exhibit enhanced reactivity relative to their unsubstituted N-alkyl counterparts, were previously suggested be more due carbamoylation -NH moiety generating an electron withdrawing effect.Probing this by structural analysis N-Boc-and N-PhF-dioxathiazinanes using NMR spectroscopy, X-ray diffraction, DFT...
Metabolism of N1-acetylspermidine and N8-acetylspermidine in rat liver kidney was studied vivo. N1-Acetylspermidine metabolized primarily to putrescine while underwent deacetylation yield spermidine. The rate metabolism these two compounds much greater than that exceeded both kidney. These rapid rates could at least part account for the low levels found tissues. differences routes may indicate cellular functions compounds.
The synthesis and biological evaluation of penicillamine(6)-5-tert-butylproline(7)-oxytocin analogs comparison with their proline(7)-oxytocin counterparts has led to the discovery two potent oxytocin (OT) antagonists: [dPen(1),Pen(6)]-oxytocin (1, pA(2) = 8.22, EC(50) 6.0 nM) [dPen(1),Pen(6),5-tBuPro(7)]-oxytocin (2, 8.19, 6.5 nM). In an attempt understand conformational requirements for activity, spectroscopic analyses 1 2 were performed using (1)H NMR, laser Raman CD techniques. H(2)O,...
Abstract Background: Effective treatment of metastatic, triple-negative breast cancer (TNBC) remains a highly unmet medical need. We have developed ES425, bispecific ADAPTIR™ (modular protein technology) molecule that redirects T-cell cytotoxicity to tumor cells expressing ROR1 (receptor tyrosine kinase-like orphan receptor 1), an oncofetal antigen expressed on TNBC and other malignancies. Results are presented for studies run examine in vitro vivo activity ES425 preclinical models TNBC....
Abstract Introduction: CD123 is a component of the IL-3 receptor expressed in several hematological malignancies including AML, ALL, HCL, and MDS. compelling target AML due to its overexpression on blasts as well leukemic stem cells, which are thought be resistant chemotherapy may responsible for relapse disease following treatment. While by some normal leukocyte populations circulation hematopoietic progenitor cells bone marrow, low frequency expression cell types provides therapeutic...