A5067447756- Protein Structure and Dynamics
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Alzheimer's disease research and treatments
- Monoclonal and Polyclonal Antibodies Research
- Lysosomal Storage Disorders Research
- Protein purification and stability
- Mass Spectrometry Techniques and Applications
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Trypanosoma species research and implications
- Bioinformatics and Genomic Networks
- Enzyme Catalysis and Immobilization
- Parkinson's Disease Mechanisms and Treatments
- Supramolecular Self-Assembly in Materials
- Prion Diseases and Protein Misfolding
- Cancer-related Molecular Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Microbial Metabolic Engineering and Bioproduction
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- Autoimmune and Inflammatory Disorders Research
- Fluid Dynamics and Heat Transfer
Denali Therapeutics (United States)
2019-2022
Amgen (United States)
2008-2017
Science Applications International Corporation (United States)
2003-2008
Center for Cancer Research
2006-2008
University of Massachusetts Amherst
2001-2006
National Cancer Institute
2004-2005
Institute for Advanced Study
2005
Tel Aviv University
2003-2005
Frederick National Laboratory for Cancer Research
2003-2004
National Institutes of Health
2003
Naturally occurring IgG antibodies are bivalent and monospecific. Bispecific having binding specificities for two different antigens can be produced using recombinant technologies projected to have broad clinical applications. However, co-expression of multiple light heavy chains often leads contaminants pose purification challenges. In this work, we modified the CH3 domain interface antibody Fc region with selected mutations so that engineered proteins preferentially form heterodimers....
Abstract Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and preclinical animal models. Here we show increased levels Dickkopf-1 (DKK-1) animals treated antibody, suggesting a negative feedback mechanism that limits Wnt-driven formation. To test our hypothesis co-inhibition both factors further mass, engineer first-in-class bispecific antibody single residue pair mutations Fab region to promote efficient stable cognate light–heavy chain pairing....
An enzyme transport vehicle enables brain delivery of lysosomal enzymes across the blood-brain barrier in mice.
Delivery of biotherapeutics across the blood-brain barrier (BBB) is a challenge. Many approaches fuse to platforms that bind transferrin receptor (TfR), brain endothelial cell target, facilitate receptor-mediated transcytosis BBB. Here, we characterized pharmacological behavior two distinct TfR-targeted fused iduronate 2-sulfatase (IDS), lysosomal enzyme deficient in mucopolysaccharidosis type II (MPS II), and compared relative exposures functional activities both mouse models. IDS...
Beta-Hairpins with short connecting loops (1-5 residues) have been identified from a data set of 250 non-homologous, high resolution (< or =2.0 A) protein crystal structures. The conformational preferences the loop segments analyzed specific aim identifying frequently occurring motifs. Type I' and II' beta-turns were found to propensity for occurrence in two residue loops. For three four loops, major motif linking is alphaR-alphaR-alphaL (type I beta-turn followed by left-handed helical...
Recent evidence suggests that amyloidogenic oligomers may be the toxic species in cell cultures. Thus, it is crucial to understand their structure and oligomerization mechanism atomistic detail. By employing tens of fast central processing units an advanced phase-space sampling algorithm, parallel-tempering molecular dynamics, we have explored energy landscape peptide explicit water. A pentapeptide, DFNKF, derived from human calcitonin its mutant, DF KF, was simulated with a total simulation...
Understanding and ultimately predicting protein associations is immensely important for functional genomics drug design. Here, we propose that binding sites have preferred organizations. First, the hot spots cluster within densely packed 'hot regions'. Within these regions, they form networks of interactions. Thus, located a region contribute cooperatively to stability complex. However, contributions separate, independent regions are additive. Moreover, often already pre-organized in unbound...
Although 8-anilinonaphthalene-1-sulfonic acid (ANS) is frequently used in protein folding studies, the structural and thermodynamic effects of its binding to proteins are not well understood. Using high-resolution two-dimensional NMR human interleukin-1 receptor antagonist (IL-1ra) as a model protein, we obtained detailed information on ANS-protein interactions absence presence urea. The ambient elevated temperatures affinity specificity ANS were assessed from experiments performed at 25...