A5084182308- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Chemical Synthesis and Reactions
- Origins and Evolution of Life
- Phenothiazines and Benzothiazines Synthesis and Activities
- Dendrimers and Hyperbranched Polymers
- Carbohydrate Chemistry and Synthesis
- Diabetes Treatment and Management
- Enzyme Structure and Function
- Monoclonal and Polyclonal Antibodies Research
- Synthetic Organic Chemistry Methods
- Synthesis and Biological Evaluation
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Pharmacological Effects and Assays
- Helicobacter pylori-related gastroenterology studies
- Ferrocene Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Amino Acid Enzymes and Metabolism
- Machine Learning in Bioinformatics
- Click Chemistry and Applications
- Regulation of Appetite and Obesity
Novo Nordisk (Denmark)
2010-2022
University of Bern
2003-2007
Royal Agricultural University
2003
Office of the Attorney General
1966
Liraglutide is an acylated glucagon-like peptide-1 (GLP-1) analogue that binds to serum albumin in vivo and approved for once-daily treatment of diabetes as well obesity. The aim the present studies was design a once weekly GLP-1 by increasing affinity secure full stability against metabolic degradation. fatty acid moiety linking chemistry were key features high receptor (GLP-1R) potency obtaining prolonged exposure action analogue. Semaglutide selected optimal candidate. has two amino...
In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological processes, such as food intake, vasoconstriction, sedation, memory retention. Here, we report the structures of human Y1, Y2, Y4 in complex with NPY or PP, Gi1 protein. These reveal distinct binding poses upon coupling different receptors, reflecting importance conformational plasticity recognizing...
Zn–proline catalyzed aldolisation of glycoladehyde gave mainly tetroses whereas in the cross-aldolisation and rac-glyceraldehyde, pentoses accounted for 60% sugars formed with 20% ribose.
Abstract The Zn–proline complex is shown to catalyze the aldol reaction of acetone and a wide range arenecarbaldehydes in aqueous media, accepting even deactivated such as methoxybenzaldehydes good yields. Enantiomeric excesses up 56 % could be obtained with 5 mol‐% catalyst at room temperature, 66 –15 °C. regio‐ stereoselective hydroxyacetone (moderate yields) dihydroxyacetone (excellent donor, 80–90 yields mmol‐equiv.). Plausible mechanisms for are discussed. (© Wiley‐VCH Verlag GmbH &...
Zn-proline catalyzes the aldolisation of unprotected glycolaldehyde in water to give tetroses and hexoses; threose (33% product mixture) was formed with 10% enantiomeric excess D-isomer.
Peptide dendrimers were investigated as synthetic models for aldolase enzymes. Combinatorial libraries prepared with active residues such lysine and proline placed at the dendrimer core or near surface. On-bead selection activity was carried out using dye-labelled 1,3-diketone 1a, suitable covalent trapping of enamine-reactive side-chains, fluorogenic enolization probe 6. Aldolase catalyzed aldol reaction acetone, dihydroxyacetone cyclohexanone nitrobenzaldehyde. Much like enzymes, exhibited...
Peptides are notoriously known to display very short in vivo half-lives often measured minutes which many cases greatly reduces or eliminates sufficient efficacy. To obtain long allowing for up once-weekly dosing regimen, fatty acid acylation (lipidation) have been used non-covalently associate the peptide serum albumin thus serving as a circulating depot. This approach is generally considered scientific and patent community standard protract almost any given peptide. However, it not trivial...
The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by zinc-proline (Zn(L-Pro)2) and secondary amines such as proline, (2S,4R)-4-hydroxyproline (Hyp) (S)-(+)-1-(2-pyrrolidinomethyl)pyrrolidine (PMP) is shown to proceed an enamine mechanism, evidenced reductive trapping the iminium intermediate, while dihydroxyacetone (DHA) general bases N-methylmorpholine (NMM) occur rate-limiting deprotonation α-carbon formation enolate intermediate.
In recent years peptide YY (PYY) has attracted attention within the area of diabetes and obesity due to its involvement in food intake regulation glucose homeostasis. It is well-known that PYY1-36 rapidly cleaved by dipeptidyl peptidase-4 more Y2 receptor selective analogue PYY3-36, which further inactive PYY3-34. order improve selectivity proteolytic stability C-terminus, we synthesized several analogues incorporating N-methyl amino acids or β-homo other non-natural acids. These were tested...
Herein we describe an algorithm for designing combinatorial peptide libraries split-and-mix synthesis on solid support that are decodable by amino acid analysis (AAA) of the beads. AAA is a standard service available in most biochemical laboratories, and it allows one to control quality each bead, important feature missing from library decoding protocols. In algorithm, AA assigned two variable positions sequence grouped "unique pair". This arrangement limits design because both number unique...
Fluorescence screening of a 96-membered SPOT library histidine containing dendritic and linear peptides revealed the remarkable esterolytic activity short oligomers that show catalytic proficiencies within one order magnitude histidine-containing esterase peptide dendrimers.
Peptide agonists acting on the glucagon-like peptide 1 receptor (GLP-1R) promote glucose-dependent insulin release and therefore represent important therapeutic agents for type 2 diabetes (T2D). Previous data indicated that an N-terminal II β-turn motif might be feature GLP-1R. In contrast, recent publications reporting structure of full-length GLP-1R have shown N-terminus receptor-bound in α-helical conformation. To reconcile these conflicting results, we prepared N-terminally constrained...
Reacting a 65,536 member combinatorial library of octapeptides on TentaGel beads with various proteases followed by selective staining the free amino termini at reacted bead surface and sequence determination acid analysis allowed rapid identification protease substrates.
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