A5027933871- Protein purification and stability
- Pancreatic function and diabetes
- Diabetes Management and Research
- RNA Interference and Gene Delivery
- Analytical Chemistry and Chromatography
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Treatment and Management
- Advanced Polymer Synthesis and Characterization
- Bacteriophages and microbial interactions
- Field-Flow Fractionation Techniques
- Drug Solubulity and Delivery Systems
- Neuropeptides and Animal Physiology
- Microfluidic and Capillary Electrophoresis Applications
- Metabolism, Diabetes, and Cancer
- Advanced Drug Delivery Systems
- Biopolymer Synthesis and Applications
- Glycosylation and Glycoproteins Research
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- thermodynamics and calorimetric analyses
- biodegradable polymer synthesis and properties
- Biochemical and Structural Characterization
- Hydrogels: synthesis, properties, applications
- Proteoglycans and glycosaminoglycans research
- Photochromic and Fluorescence Chemistry
Novo Nordisk (Denmark)
2010-2024
Novo Nordisk (United Kingdom)
2012
Novozymes (Denmark)
2008
Lund University
2002-2004
Lomonosov Moscow State University
2003
Basal insulins with improved kinetic properties can potentially be produced using acylation by fatty acids that enable soluble, high-molecular weight complexes to form post-injection. A series of insulins, acylated at B29 via glutamic acid spacers, were examined deduce the structural requirements.Self-association, molecular masses and hexameric conformations studied size exclusion chromatography monitored UV or multi-angle light scattering dynamic scattering, circular dichroism spectroscopy...
An orally delivered GLP-1 analog coformulated with the absorption enhancer SNAC achieves transcellular-directed in stomach.
We report the crystal structure of two variants Drosophila melanogaster insulin-like peptide 5 (DILP5) at a resolution 1.85 Å. DILP5 shares basic fold insulin family (T conformation) but with disordered B-chain C terminus. dimerizes in and solution. The dimer interface is not similar to that observed vertebrates, i.e. through an anti-parallel β-sheet involving termini but, contrast, formed N termini. binds activates human receptor lowers blood glucose rats. It also trehalose levels...
To study the self-association states of insulin degludec and aspart alone combined in pharmaceutical formulation under conditions simulating subcutaneous depot.Formulations were made 0.6 mM at 3 5 Zn/6 monomers, (2 monomers). Self-association was assessed using size-exclusion chromatography (SEC) monitored by UV orthogonal reverse-phase chromatography.Simulating formulation, eluted as dihexamers, whereas hexamers monomers. Combining low zinc with increased dihexamer content, indicating...
Abstract Metal chelate affinity precipitation (MCAP) has been successfully developed as a simple purification process for proteins that have metal ions. The present lack of widespread applications this technique compared to immobilized chromatography (IMAC) may be related the scarcity well‐characterized macroligands (AML) and their number different systems. In work we describe detailed study new system using metal‐loaded thermoresponsive copolymers AML. vinylimidazole (VI) with N...
Several studies have shown that adiponectin can lower blood glucose in diabetic mice. The aim of this study was to establish an effective production process and evaluate the anti-diabetic potential different forms mice sand rats.Human high molecular weight, mouse low weight plus human globular were expressed purified from mammalian cells or yeast. protein administered at 10-30 mg/kg i.p. b.i.d. db/db for 2 weeks. Furthermore, batches 5-15 rats 12 days.Surprisingly, none our had any effect on...
Recently, a new class of copolymers, so-called protein-like copolymers has been predicted theoretically by computer simulation. In these the conformation copolymer determines exposure certain comonomer units to outer solution. Depending on conformation, molecules with essentially same composition could have pronouncedly different properties. The authors demonstrated experimentally such behavior in case poly[(N-vinylcaprolactam)-co-(N-vinylimidazole)] (Dokl. Chem. 2001, 375, 637). One more...
Factors affecting phase separation in water−salt solutions of polyelectrolyte complexes (PECs), formed by DNA and integral or pendant polycations with a quaternary amino group every monomer unit, have been studied. When no salt was added, quantitative precipitation occurred at stoichiometric charge ratio, φ = [+]/[−] ≈ 1. In mixtures poly(N,N'-dimethyldiallylammonium chloride) (PDMDAAC, polycation), insoluble PECs the range 0.7 < 2. This suggests formation soluble, negatively charged 0...
The demand for highly purified plasmids in gene therapy and plasmid-based vaccines requires large-scale production of pharmaceutical-grade plasmid. Large-scale purification plasmid DNA from bacterial cell culture normally includes one or several chromatographic steps. Prechromatographic steps include precipitation with solvents, salts, polymers combined enzymatic degradation nucleic acids. No method alone has so far been able to selectively capture directly a clarified alkaline lysate. We...
Lys(B29)(N(ε)ω-carboxyheptadecanoyl) des(B30) human insulin is an analogue belonging to a class of analogues designed form soluble depots in subcutis by self-association, aiming at protracted action. On the basis small angle X-ray scattering (SAXS) supplemented range biophysical and structural methods (field flow fractionation, dynamic multiangle light scattering, circular dichroism, size exclusion chromatography, crystallography), we propose mechanism for self-association expected occur...
A divergent protein synthesis strategy was executed to effectively synthesize Bowman–Birk protease inhibitor (BBI) analogues using native chemical ligation of peptide hydrazides. Grafting selected residues from a potent trypsin inhibitor, sunflower inhibitor-1, onto the α-chymotrypsin-binding loop BBI, resulted in fourfold improvement α-chymotrypsin inhibition. The crystal structure synthetic BBI analogue co-crystallized with confirmed correct fold and showed similar overall unmodified...
Here, we describe the development of FGF21 analog zalfermin (NNC0194-0499, 15), intended for once-weekly sc dosing. Protein engineering was needed to address inherent druggability issues natural hormone. Thus, deamidation Asp121 solved by mutation glutamine, and oxidation Met168 leucine. N-terminal region degradation dipeptidyl peptidase IV prevented alanine residue elongation. To prevent inactivating metabolism fibroblast activation protein carboxypeptidase-like activity in C-terminal...
Abstract Formation of insoluble polyelectrolyte complexes (PECs) between RNA and polycations was followed by measuring the residual absorbance in solution after separation precipitate. The studied were poly( N , N′ ‐dimethyldiallylammonium) chloride (pendant type) 2,5‐ionene bromide (integral with quaternary amino groups every monomer unit. data obtained compared results analogous studies DNA‐containing PECs. This study is a part project aimed at specific plasmid DNA from RNA, major problem...
Monoclonal antibodies (mAbs) are often formulated as high-protein-concentration solutions, which in some cases can exhibit physical stability issues such high viscosity and opalescence. To ensure that mAb-based drugs meet their manufacturing, stability, delivery requirements, it is advantageous to screen for select mAbs during discovery not prone behaviors. It has been recently shown both these macroscopic properties be predicted a certain extent from the diffusion interaction parameter...
Current oral formulations of macromolecules including peptides typically rely on single permeation enhancer (PE) to promote absorption and thus bioavailability. In this work, we combined two PEs, namely sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) caprate (C10), in one tablet formulation potentially gain a synergistic effect for enhanced gastric GLP-1 analogue PCSK9 inhibitor. Permeability tests organoids-based cell model showed that the combination SNAC C10 can significantly...
Recently, a new class of copolymers, so-called protein-like copolymers has been predicted theoretically by computer simulation. In these the conformation copolymer determines exposure certain comonomer units to outer solution. Depending on conformation, molecules with essentially same composition could have pronouncedly different properties. The authors demonstrated experimentally such behavior in case poly[(N-vinylcaprolactam)-co-(N-vinylimidazole)] (Dokl. Chem. 2001, 375, 637). One more...