A practical reference on deamidation: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-04-09. Anything still debated is marked as such rather than presented as settled.
Lyophilised semaglutide is generally held at -20 °C or below, protected from light and moisture. Reconstituted solutions are typically kept at 2-8 °C and used within a defined window because degradation accumulates over time. Repeated freeze-thaw cycles are discouraged, since each cycle can promote aggregation and reduce monomeric content. Room-temperature stability of the solid has been examined in some studies but remains incompletely characterised for long durations, so cold storage is the conservative default for research material.
Degradation proceeds along several parallel routes. Deamidation of asparagine and glutamine residues generates charged variants that shift retention time in chromatographic analysis. Oxidation targets methionine and can be accelerated by trace metals or dissolved oxygen. Non-covalent aggregation produces dimers, oligomers, and larger species that are difficult to reverse. Isomerisation at aspartate residues is slower but measurable under thermal stress. The distribution among these pathways depends on pH, buffer composition, ionic strength, and the presence of excipients such as sugars or surfactants.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L-cells after food intake. It contains 31 amino acids and differs from native GLP-1 through modifications that slow enzymatic breakdown. The peptide was developed to extend the short circulating half-life of endogenous GLP-1, which is measured in minutes. Researchers introduced the compound in the early 2010s. Two backbone changes and a fatty acid side chain define its structure, distinguishing it from earlier GLP-1 receptor agonists.
The compound binds the GLP-1 receptor on pancreatic beta cells and other tissues, activating a G-protein signaling cascade that raises intracellular cyclic AMP. This action increases glucose-dependent insulin secretion when blood glucose is elevated, while binding also slows gastric emptying and reduces glucagon release. In the central nervous system, receptor activation in the hypothalamus and brainstem contributes to reduced appetite. The fatty acid chain binds albumin, which protects the peptide from renal filtration and enzymatic degradation. This albumin binding is central to its extended circulation time.
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white lyophilised powder | visual inspection of solid |
| Solubility | Freely soluble in water, pH dependent | buffer choice affects clarity |
| Typical storage | -20 °C, desiccated, protected from light | solution form kept at 2-8 °C |
| Primary purity method | RP-HPLC with UV detection, 214-220 nm | reported as area percent |
| Identity confirmation | LC-ESI-MS, approximately 4114 Da | compared with theoretical mass |
Reversed-phase high-performance liquid chromatography with ultraviolet detection is the dominant approach for peptide purity assessment, usually paired with mass spectrometry to confirm molecular mass and sequence. Peptide mapping by enzymatic digestion and tandem mass spectrometry locates modifications such as deamidation and oxidation. Quantitation in plasma matrices can be performed by LC-MS/MS after solid-phase extraction. Method validation follows general guidance on accuracy, precision, linearity, and limits of detection. Comparability of results between laboratories, when no shared reference standard is available, remains an open question.
Stability studies focus on deamidation of asparagine and glutamine residues, oxidation of methionine, and aggregation into higher-order species. The fatty acid side chain adds susceptibility to oxidative change and can promote self-association at high concentration. Lyophilised material is comparatively robust when kept cold and dry, while aqueous solutions require refrigeration and protection from light. Forced degradation experiments under heat, acid, base, and peroxide conditions establish the specificity of each analytical method. Which degradation route dominates under real storage conditions depends on the formulation and stays formulation-specific.
Reversed-phase high-performance liquid chromatography is widely used to assess purity and to separate the parent peptide from related substances. Mass spectrometry confirms identity and can resolve modifications that differ by a few daltons. Size-exclusion chromatography detects dimers and higher aggregates, which are relevant to both stability and immunogenicity questions. Peptide mapping with enzymatic digestion locates specific modifications along the sequence. Circular dichroism provides a secondary-structure profile, although it gives limited information about local conformational changes.
Quality control for peptide material focuses on identity, purity, content and the profile of impurities. Common degradants include deamidated and oxidised forms, plus aggregates formed during storage or handling. Forced degradation studies under heat, light, acid and peroxide help define which conditions accelerate change and which analytical methods detect it. Limits for individual impurities are set by pharmacopoeial monographs or manufacturer specifications. How much a given impurity affects biological activity is often uncertain, and conclusions may depend on the assay used.
The two substrates of this enzyme are glycerol and oxidised nicotinamide adenine dinucleotide phosphate (NADP+). Its products are glycerone, reduced NADPH, and a proton. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is glycerol:NADP+ 2-oxidoreductase (glycerone-forming). Other names in common use include dihydroxyacetone reductase, dihydroxyacetone (reduced nicotinamide adenine dinucleotide, phosphate) reductase, dihydroxyacetone reductase (NADPH), DHA oxidoreductase, and glycerol 2-dehydrogenase (NADP+). This enzyme participates in glycerolipid metabolism.
danofloxacin – 2nd gen, related to ciprofloxacin difloxacin – 2nd/3rd gen, related to temafloxacin enrofloxacin – 2nd gen, metabolizes into ciprofloxacin ibafloxacin – 3rd gen, related to levofloxacin marbofloxacin – 3rd gen, related to levofloxacin orbifloxacin – 3rd gen, related to sparfloxacin sarafloxacin – 2nd/3rd gen, related to difloxacin pradofloxacin – 3rd gen
==== Protease inhibitors ==== Protease inhibitors are a class of compounds that inhibit the activity of proteases (enzymes responsible for cleaving peptide bonds in proteins). These inhibitors are crucial in various biological processes and therapeutic applications, as proteases play key roles in numerous physiological functions, including digestion, immune response, blood coagulation, and cell signaling. An extracellular cysteine protease inhibitor, ECPI-2, was purified from the culture medium of Chlorella sp. The inhibitor had an inhibitory effect against the proteolytic activity of papain, ficin, and chymopapain. ECPI-2 contains 33.6% carbohydrate residues that may be responsible for the stability of the enzyme under neutral or acidic conditions. These inhibitor proteins from Chlorella may be synthesized to protect cells from attacks by e.g., viruses or herbivores. Compared to organic compounds, peptide drugs are of relatively low toxicity to the human body. The development of peptide inhibitors as drugs is thus an attractive research topic in current medicinal chemistry. Protease inhibitors are attractive agents in the treatment of specific diseases; for instance, elastase is of critical importance in diseases like lung emphysema, which motivates further investigation on microalgal protease inhibitors as valuable lead-structures in pharmaceutical development.
Sources: en.wikipedia.org
=== Rail === Bromley is served by two main rail stations. Bromley South provides National Rail services to London Victoria (non stop, semi fast via Denmark Hill and stopping services via Herne Hill), London Blackfriars via Catford, Orpington, Sevenoaks via Swanley, Ramsgate via Chatham, Dover Priory via Chatham & Canterbury East and to Ashford International via Maidstone East. Bromley North provides shuttle services to Grove Park, where onward connections can be made for services to London Charing Cross & London Cannon Street via Lewisham. Finally, Shortlands railway station serves primarily residential areas immediately southwest of the town centre. Being one stop west of Bromley South, Southeastern and Thameslink services connect the station to London Victoria and London Blackfriars.
== Function == The broad distribution of relaxin-3 fibres/RXFP3 within several key neuronal circuits suggests an ability to modulate a broad range of behaviours. This has been confirmed in a growing number of rodent studies, which demonstrate relaxin-3 is able to modulate arousal, the response to stress, feeding/metabolism and memory; and likely plays a role in the generation/regulation of hippocampal theta rhythm.
The word frankfurter comes from Frankfurt, Germany, where pork sausages similar to hot dogs originated. These sausages, Frankfurter Würstchen, were known since the 13th century and given to the people on the event of imperial coronations, starting with the coronation of Maximilian II, Holy Roman Emperor, as King. "Wiener" refers to Vienna, Austria (German: Wien), home to a sausage made of a mixture of pork and beef. Johann Georg Lahner, an 18th/19th century butcher from the Franconian city of Coburg, is said to have brought the Frankfurter Würstchen to Vienna, where he added beef to the mixture and simply called it Frankfurter. Nowadays, in German-speaking countries, except Austria, hot dog sausages are called Wiener or Wiener Würstchen (Würstchen means "little sausage"), to differentiate them from the original pork-only mixture from Frankfurt. In Swiss German, it is called Wienerli, while in Austria the terms Frankfurter or Frankfurter Würstel are used.
Sources: en.wikipedia.org
== Side effects == The most prevalent side effects for endoxifen include headache, vomiting, insomnia. Other side effects were: gastritis, epigastric discomfort, diarrhea, restlessness, somnolence, etc. Some of the adverse events reported with other therapies for the management of manic episodes of bipolar I disorder were not observed during the clinical development program of endoxifen like reduction in platelet count, change in blood thyroid-stimulating hormone levels. There were no deaths, serious or significant adverse events during the conduct of trials. Overall, endoxifen was found to be well-tolerated and safe in patients of bipolar I disorder with acute manic episodes with or without mixed features. An important caveat here is that the trial was of very short duration (only three weeks). The long-term safety of Endoxifen has not been established among patients with Bipolar Disorder.
=== First isolation of DNA === Working in the 19th century, biochemists initially isolated DNA and RNA (mixed together) from cell nuclei. They were relatively quick to appreciate the polymeric nature of their "nucleic acid" isolates, but realized only later that nucleotides were of two types—one containing ribose and the other deoxyribose. It was this subsequent discovery that led to the identification and naming of DNA as a substance distinct from RNA. Friedrich Miescher (1844–1895) discovered a substance he called "nuclein" in 1869. Somewhat later, he isolated a pure sample of the material now known as DNA from the sperm of salmon, and in 1889 his pupil, Richard Altmann, named it "nucleic acid". This substance was found to exist only in the chromosomes. In 1919 Phoebus Levene at the Rockefeller Institute identified the components (the four bases, the sugar and the phosphate chain) and he showed that the components of DNA were linked in the order phosphate-sugar-base. He called each of these units a nucleotide and suggested the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule. However Levene thought the chain was short and that the bases repeated in the same fixed order. Torbjörn Caspersson and Einar Hammersten showed that DNA was a polymer.
=== Fluorescence recovery after photobleaching === Fluorescence recovery after photobleaching (FRAP) is a photochemical process applied to fluorophores when they lose their fluorescent properties. It can be used to measure the viscosity and lateral diffusion of a lipid bilayer. It also rejuvenates the fluorescence of the fluorophore and monitors how long this process takes to occur over time.
6 August Weather Forecast about weather forecasting in the UK; Swedish Lennart Bengtsson of the European Centre for Medium-Range Weather Forecasts; Alistair Woodroffe and Brian Webster of the Met Office; numerical calculations began in the early 1950s with computers making 10,000 calculations a second but by the mid-1980s it was one billion; Meteosat-2 launched in June 1981; Steven Burke of the London Potato Futures Association; Capt Derek Ralph in a British Caledonian BAC One-Eleven flying to Aberdeen Airport; amateur weatherman Bill Foggitt; the weather centre and Lockheed C-5 Galaxy aircraft at RAF Mildenhall; conservationist Robin Page; narrated by Muriel Gray, directed by John Dollar, made by Uden Associates 13 August Made to Measure, essentially a re-edited, slightly updated edition of the August 1986 episodes on the F1 Ford turbocharged engine, with a few minutes of new content; in May 1987 Peter Collins watches the previous San Marino Grand Prix; Ford Cosworth V6 B187 cars: engine mapping; Dick Scammel, general head of engineering; Martin Walters, chief development engineer; the engine is dismantled, and damage is found; Geoff Goddard, chief racing engine designer; electromagnetic pulses from the engine affected the working of the engine computer circuitry; rogue signals were picked up by the engine computer, so causing erratic fuel injection; French F1 driver Patrick Tambay listens to the sound of the turbo; the turbo pressure would be limited to 2.5 in 1988, before turbos were banned for the 1989 season; the Italian Grand Prix circuit; each team is allowed two sets of qualifying tyres; the tyres on the rear axle warm up before the front axle; the Honda V6 engine could produce 1200 hp; chief designer Rory Byrne, and F1 aerodynamic forces. Narrated mostly by Martin Jarvis and partly by Eleanor Bron 20 August Twang, Bang, Kerang!, about the electric guitar; the Fat Tuesdays night club, and Les Paul; Glenn Wilson of the Institute of Psychiatry in London; Louis Jordan in the late 1940s; Charlie Christian developed the Gibson-ES150; Steve Howe of Yes; Burns London manufacturing guitars; Dave Russell; the body of the guitar was made of maple, a tonewood, and the fretboard of rosewood; the sound originates from the type of wood; Jerry Donohue of Fairport Convention; pickups made by Seymour Duncan; Chet Atkins; Andy Summers of The Police and Every Breath You Take; Francis Dunnery of It Bites, and Once Around the World. Narrated by John Hedges, produced by Patrick Uden, directed by Jeremy Llewellyn-Jones, made by Uden Associates 27 August What Goes Up..., about dismantling the AGR at Sellafield; it featured Tom Marsham CBE FRS (10 November 1923 – 12 October 1989) of UKAEA at Risley, Warrington (Birchwood Park), who was the reactor manager of Calder Hall in 1956. Narrated by Sue Jay, produced by Michael Blakstad, made by Workhouse Productions 3 September Hole in the Sky, about the depletion of the ozone layer, with Sir Bob Watson at NASA; the NERC's British Antarctic Survey had been measuring ozone levels since 1957 at the Halley Research Station, and a team led by Joe Farman noticed a hole in the layer; NASA had not noticed an ozone hole on its Nimbus 7 satellite, although the satellite had picked up all of the data, as Richard Stolarski of the Goddard Space Flight Center found; the ozone hole was caused by the polar vortex over the winter, where air movements outside of Antarctica are trapped, and there is not enough light to form new ozone; some people believed that the 1982 Mexican El Chichón volcanic eruption was to blame; in 1974 F. Sherwood Rowland and Mario Molina of the University of California, Irvine found that some chlorine compounds would destroy ozone by making chlorine monoxide, and both received the 1995 Nobel Prize in Chemistry for this discovery; the Chemical Manufacturers' Association (since 2000 the American Chemistry Council) and the National Science Foundation launched a new atmospheric survey at McMurdo Station, led by Susan Solomon of the Earth System Research Laboratories; Jerry D. Mahlman of the Geophysical Fluid Dynamics Laboratory at Princeton was attempting a computer model of the Antarctic atmosphere; Rafe Pomerance of the World Resources Institute; the greenhouse effect, described by James Hansen of the Goddard Institute for Space Studies, who claimed that the Earth's temperature would be 2 degrees higher by 2000, 3 degrees higher by 2010, and 4 to 7 degrees warmer by 2030; Richard E. Benedick. Directed by Linda Harrar, produced by Paula Apsell, made by WGBH, Uden Associates, Television Trust for the Environment and Sveriges Television. Originally a Nova documentary 24 September Dirty Money, about whether the environment can be cleaned up; the UK's first anti-pollution trade fair in March 1987, attended by William Waldegrave; Father Jim Conlon and Portglenone Abbey in N Ireland, with an anaerobic digester, which saved £1000 a month in gas cost, and the manure was sold for £25,000 a year; Mike Flux of ICI; biologist Paul Johnston of Greenpeace, in Teesside; the River Tees was the second-most polluted in the UK, with Douglas Ord of Northumbrian Water; Ken Murphy, and how Greenpeace attempted to block an effluent pipe near Immingham in March 1985; John Elkington, environmental writer; BioTechnica of Llanishen in Cardiff, reclaiming contaminated land on a former highly polluted gasworks site in Lancashire; Jutta Ditfurth; Hans-Georg Peine of BASF AG, and the Sandoz chemical spill in November 1986 in Switzerland; in 1983, ICI founded the first bioplastic company, called Marlborough Biopolymers, which made polyhydroxy butyrate; Dame Anita Roddick of The Body Shop, who worked with Friends of the Earth; Peter Baylis of the NERC Environmental Satellite Laboratory, which began in 1975, in the University of Dundee's Ewing Building, and largely provided the only UK archive of satellite environmental data. Narrated by Bob Peck, produced by Edward Poulter, directed by David Sharp, made by London Scientific Films 1 October Malltime. A US production, produced by Mike Wallington, made by George Haggerty, made by Kai Productions 8 October Anything You Can Do..., about new robotics; the five houses puzzle; Richard Gregory, professor of neuropsychology at the University of Bristol; Roger Mathias of Plessey Radar and the Multi-function Electronically Scanned Adaptive Radar (MESAR), began in 1982; Henry Thompson and speech recognition at the School of Informatics, University of Edinburgh; Robert Kowalski of the Department of Computing, Imperial College London; Margaret Boden of the University of Sussex; J. Michael Brady; Paul Caplin and robotics; Roy Bottomley of Meiko Scientific, and the transputer, developed in the UK; Plessey Laboratories at the Allen Clark Research Centre, and new chemical compounds for computer chip; logic programming and heuristics; the European Eureka Prometheus Project, an expert system. Narrated by Miriam Margolyes, produced by Michael Blakstad, directed by Catherine Robins, made by Workhouse Productions 22 October Command and Control, the chain of command of nuclear weapons; it featured the Air Force Research Laboratory. Directed by Clive Syddall, made by Twenty Twenty Vision 5 November Earthquake Country, about the San Andreas fault; Robert Wallace, chief scientist of the USGS; the 1906 earthquake caused the tectonic planes to move around seven metres; geologist Grove Karl Gilbert; an earthquake in the middle section of the fault was expected for around 1988; a 5.8 earthquake on 8 June 1934; geologist Kerry Sieh and paleoseismology; if an earthquake took place, coordination would be from the Joint Forces Training Base - Los Alamitos; earthquake engineer George W. Housner of Caltech; structural engineer Ray William Clough; earthquake engineer Luis Estava Maraboto of the Engineering Institute of the National Autonomous University of Mexico. Produced by Arabella Woods, directed by John Tchalenko, made by Red Rooster Films 12 November Nature's Technology, about the different types and the modelling of animal locomotion, and legged robots; robotic hands and bioengineer Stephen Jacobsen of the University of Utah; snake-arm robots; the 1986 Adaptive Suspension Vehicle (ASV) of Ohio State University, a hexapod robot, and Vincent Vohnout; active balance and Marc Raibert; the 1965 Walking Truck of General Electric; static stability and the Odex 1 six-legged robot; biomechanics and Robert McNeill Alexander, Professor of Zoology; WABOT-2 of Waseda University, optical music recognition and the NHK Symphony Orchestra of Japan conducted by Yuzo Toyama. Narrated by Adrienne Posta, directed by David Barlow, produced by Karl Sabbagh, made by InCA 19 November Britain Can Make It?, about making kitchen units in the UK and in Germany; the dual system of apprenticeship in Germany; Sig Prais of the National Institute of Economic and Social Research; the Britain Can Make It exhibition, where the fitted kitchen was first introduced in the UK; the Hungarian designer George Fejer was largely responsible for introducing fitted kitchens; Wolfgang Luckhaus of Poggenpohl of Germany, which also developed the fitted kitchen; in the 1960s the Germans introduced chipboard for kitchen manufacturing, which became industry-standard, with wipe-clean melamine resin facing (MFC); Hilary Steedman of the NIESR, and how the Germans built kitchens to order, whereas British companies simply built kitchens, whether ordered or not; Heal's of London introduced German kitchens to the UK in the early 1970s, in a hausfest; the German SieMatic kitchen company; Doug Gregory started The Symphony Group in 1970 after seeing chipboard, developing flatpack kitchen units, the Germans did not make flatpack kitchens, only assembled kitchens; David Love, buying director of MFI, which was helped by the flatpack revolution, but it was all largely an imitation of German products, and was a mostly standard product range; Symphony introduced computer production control in the 1980s, which the Germans had introduced in the early 1970s - this allowed much more variation of manufacturing to order, which was the main German method; employees of Symphony were largely unskilled, but German workers were largely skilled apprentices, who had passed exams in manufacturing; nearly all of German kitchens were built to order, so needed skilled workers; Walter Siekmann, production manager of Poggenpohl; German furniture manufacture was found in East Westphalia (Ostwestfalen); the Germans believed in more thorough technical training, and sold their products all over the world, but British companies had less-thorough training, and did not sell as worldwide as the Germans. Narrated by John Woodvine, directed by David Habakkuk, made by Riverside Television 26 November At the Edge, about the physical limits placed upon fighter pilots when flying high G capable modern aircraft, such as the F16 and the F18. Pilots are subjected to G-LOC in the Aerospace Medicine centrifuge in San Antonio, Texas. Narrated by Ray Brooks, written, produced and directed by Chris Haws, made by InCA
Sources: en.wikipedia.org
Reverse-phase high-performance liquid chromatography with ultraviolet detection is the usual choice, with results reported as area percent. Complementary methods such as size-exclusion chromatography and mass spectrometry are needed because a single separation cannot resolve every impurity class. Purity figures are therefore method dependent and should always be read alongside the technique used.
Oxidation mainly affects methionine residues and is promoted by dissolved oxygen, trace transition metals, and prolonged exposure to light. Buffer choice and the presence of antioxidants in a formulation can alter the rate appreciably. Because the products differ in mass by only a few units, mass spectrometry is often required to detect them.
Published data on long-term ambient stability are limited, so the question remains open rather than settled. Short excursions during transport are common in practice, and many suppliers use insulated packaging with cold packs. Where stability data are absent, cold-chain handling with temperature logging is the safer approach.
It is a synthetic analog of GLP-1 produced through medicinal chemistry to resist enzymatic degradation. The design goal was longer circulation than the native hormone.