A practical reference on deamidation: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-06-29. Anything still debated is marked as such rather than presented as settled.
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.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 nm is the standard purity method, reported as area percent. Mass spectrometry, usually with electrospray ionisation, confirms identity and reveals covalent modifications. Size-exclusion chromatography quantifies aggregates and fragments. Peptide mapping after enzymatic digestion localises changes to specific sequence regions. Circular dichroism and infrared spectroscopy report on secondary structure, while light scattering tracks particle formation in liquid formulations. No single technique captures every quality attribute.
Clinical studies of semaglutide generally measure glycated hemoglobin, fasting plasma glucose, body weight, and composite cardiovascular endpoints. The SUSTAIN program enrolled adults with type 2 diabetes, while the STEP program focused on obesity without diabetes. Administration follows a stepwise escalation schedule designed to limit gastrointestinal effects during the first weeks. Reported outcomes include mean percentage weight change, the proportion of participants reaching defined weight-loss thresholds, and rates of nausea, vomiting, and diarrhea. Long-term data on durability after treatment stops are still limited and remain a topic of ongoing research.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, developed by Novo Nordisk and first approved in 2017 for type 2 diabetes. It belongs to the incretin mimetic class, a group of agents that reproduce the glucose-dependent actions of endogenous GLP-1. The molecule was engineered to resist degradation by dipeptidyl peptidase-4 and to bind serum albumin, extending its half-life from minutes to roughly one week. Approval for chronic weight management followed in 2021, based on large cardiovascular and obesity outcome trials.
| 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 |
Storage conditions for semaglutide depend heavily on the presentation. Lyophilized research powder is generally kept at two to eight degrees Celsius in a sealed container, protected from light and moisture. Manufacturer labeling for finished injectable products specifies refrigeration before first use, with defined in-use periods at room temperature afterward. The oral tablet form is stored at controlled room temperature and is more tolerant of short excursions. Temperature excursions should be documented rather than inferred.
Peptide degradation follows several routes. Hydrolysis cleaves the backbone at susceptible residues, oxidation targets methionine and tryptophan side chains, and aggregation produces higher-molecular-weight species that are difficult to reverse. Light exposure accelerates oxidation, which is why amber glass or opaque secondary packaging is common. Repeated freeze-thaw cycles promote aggregation and are best avoided. Stability-indicating methods detect these changes before they become visible.
Quality control for research material typically involves reversed-phase HPLC for purity and identity, mass spectrometry for molecular weight confirmation, and Karl Fischer titration for residual water content. Peptide content is often reported as the mass of actual peptide rather than total powder mass, since counterions and water contribute to the latter. A certificate of analysis should list the method used for each specification. Limits and acceptance criteria vary by supplier and by intended application.
Quantification and purity assessment rely on separation methods coupled to optical or mass detection. Reversed-phase high-performance liquid chromatography resolves the intact peptide from related impurities and is the standard assay technique. Size-exclusion chromatography measures aggregates, while ion-exchange chromatography separates charge variants produced by deamidation. Mass spectrometry confirms identity and detects mass shifts of a few daltons. In biological matrices, liquid chromatography with tandem mass spectrometry is often used because immunoassays can cross-react with endogenous GLP-1 or with circulating fragments.
As a peptide, semaglutide is sensitive to conditions that break amide bonds or modify side chains. Deamidation of asparagine and glutamine residues, oxidation of methionine and tryptophan, and non-covalent aggregation are the main degradation routes described in published stability work. Rate depends strongly on pH, buffer species, ionic strength, temperature and exposure to light. Formulators therefore choose a defined solution pH and often add excipients such as phosphate buffer, propylene glycol and phenol, each of which plays a separate role in pH control, tonicity or preservation.
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.
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.
==== Lieutenant of the Royal Victorian Order (LVO) ==== Ian Scott Anderson, , Director, The Duke of Edinburgh's Commonwealth Study Conferences. Mark Appleby, Crown Jeweller. Colonel Jeremy David Bagshaw, , Late Coldstream Guards, 534873; lately Chief of Staff, London District, on the occasion of the Coronation of Their Majesties The King and The Queen. Major Grant Vincent Ashley Baker, Gentleman Usher to His Majesty The King. Paul David Baumann, , Receiver-General, Westminster Abbey, on the occasion of the Coronation of Their Majesties The King and The Queen. Charles Harcourt James Davies, , Private Secretary to The Princess Royal. Karen Ross Findlay, Commander, Metropolitan Police Service, on the occasion of the Coronation of Their Majesties The King and The Queen. Dr Michael Terence Isaac, Occupational Health Advisor to the Royal Household. Air Vice-Marshal Richard Howard Lacey, , lately Gentleman Usher to His Majesty The King. Charlotte Elizabeth Martin, , Deputy Head of Ceremonial, Royal Household. Jonathan David Rogerson Martin, Director of Ceremonials, Department for Culture, Media and Sport, on the occasion of the Coronation of Their Majesties The King and The Queen. Ian Donald McCowan, lately Secretary to the Governor-General of Canada. Professor Paul Mealor, Music Advisor, Honours of Scotland Service. Graham Paul Midgley, Head of Royal Travel, Royal Household. Gavin Donald Reid, Music Advisor, Honours of Scotland Service. Paul John Sedwick, Deputy Ranger, Windsor Great Park.
The basic qualification for becoming a clinical biochemist, clinical immunologist or clinical microbiologist is a good honours degree in an appropriate subject: for clinical biochemistry, that subject might be biochemistry or chemistry (or another life science subject which contains a substantial biochemistry component); for clinical immunology, that subject might be any life science degree with an immunology component; for clinical microbiology, that subject might be any life science degree with a microbiology component. Although not essential, some candidates will apply with higher degrees in an attempt to improve their chances of selection for training and several universities currently offer MSc courses in clinical biochemistry, Immunology and Microbiology which have been approved by the ACB or the AHCS. Full-time and 'sandwich' courses are available, and further information may be obtained from individual programmes, although the level of financial support provided varies, and should be clarified at interview. Some entrants to the profession will already have obtained a PhD, and the training and research experience that this provides is invaluable to the work of the clinical scientist. In larger departments, there may be opportunities to study for a research degree after entering the profession and acquiring registration, but since this has to be fitted in with other responsibilities, it may take some years to complete.
== Pathophysiology of Skin Tension == Skin turgor is directly regulated by the volume of interstitial fluid and the structural integrity of the extracellular matrix within the dermal layer. Under normal physiological conditions, hydrostatic pressure within the capillaries pushes water into the surrounding tissue spaces, keeping the dermis plump and pressurized. When systemic fluid loss occurs, the body pulls water out of the interstitial spaces to maintain blood pressure and intravascular volume. This drop in interstitial fluid pressure strips the skin of its internal tension, causing the collagen and elastin fibers to lose their structural support and stick togetehr when deformed.
=== Neovascular glaucoma === Anti-VEGF agents as injectable medications, along with other standard of care treatment for decreasing intraocular pressure, may improve pressure in people with neovascular glaucoma for short periods. Evidence suggests that this improvement may last 4–6 weeks. There is no sufficient evidence to suggest that anti-VEGF medications are effective either for short-term or for longer-term treatment. The short, medium, and long-term safety of anti-VEGF treatment has not been well investigated.
Type V – Having the same clinical features as type IV, it can be clinically distinguished by observing a "mesh-like" appearance to a bone biopsy under a microscope. Type V can be further distinguished from other types of OI by the "V triad": an opaque band (visible on X-ray) adjacent to the growth plates; hypertrophic calluses (abnormally large masses of bony repair tissue) which form at fracture sites during the healing process; and calcification of the interosseous membrane of the forearm, which may make it difficult to turn the wrist. Other features of this condition may include pulled elbow, and, as in other types of OI, long bone bowing and hearing loss. Cases of this type are caused by mutations in the IFITM5 gene on chromosome 11p15.5. The separation of type V from type IV OI, its clinical type, was initially suggested even before its genetic cause was known, by Glorieux et al. in 2000. Type V is relatively common compared to other genetically defined types of OI—4% of OI patients at the genetics department of the Brazilian Hospital de Clínicas de Porto Alegre were found to have it. Type VI – With the same clinical features as type III, it is distinguished by bones which have an appearance similar to that seen in osteomalacia. Type VI is caused by a loss-of-function mutation in the SERPINF1 gene on chromosome 17p13.3. Type VII – OI caused by a mutation in the gene CRTAP on chromosome 3p22.3; clinically similar to OI types II and III, depending on affected individual.
Sources: en.wikipedia.org
Autoantibody testing: Many autoimmune diseases are characterized by the presence of autoantibodies. Blood tests can identify these antibodies, which are directed against the body's own tissues. For example, antinuclear antibody (ANA) testing is commonly used in the diagnosis of systemic lupus erythematosus and other autoimmune diseases. Complete Blood Count: Blood counts can provide valuable information about the number and characteristics of different blood cells, which can be affected in some autoimmune diseases. C-Reactive Protein and Erythrocyte Sedimentation Rate: These tests measure the levels of inflammation in the body, which is often elevated in autoimmune disorders. Organ-specific tests: Certain autoimmune diseases target specific organs, so tests to evaluate the function of these organs can aid in diagnosis. For example, thyroid function tests are used in diagnosing autoimmune thyroid disorders, while a biopsy can diagnose coeliac disease by identifying damage to the small intestine.
Stiffness and elasticity also guide cell migration, this process is called durotaxis. The term was coined by Lo CM and colleagues when they discovered the tendency of single cells to migrate up rigidity gradients (towards more stiff substrates) and has been extensively studied since. The molecular mechanisms behind durotaxis are thought to exist primarily in the focal adhesion, a large protein complex that acts as the primary site of contact between the cell and the ECM. This complex contains many proteins that are essential to durotaxis including structural anchoring proteins (integrins) and signaling proteins (adhesion kinase (FAK), talin, vinculin, paxillin, α-actinin, GTPases etc.) which cause changes in cell shape and actomyosin contractility. These changes are thought to cause cytoskeletal rearrangements in order to facilitate directional migration.
Donkey Kong Country for the SNES helped Nintendo's comeback against Sega. Doom, released 1993, helped drive adoption of IBM PC compatibles as a major video gaming platform. By late 1995, it was estimated that Doom was installed on more computers than the Microsoft Windows operating system. Myst and The 7th Guest, both released in 1993, drove adoption of CD-ROM drives for personal computers. Virtua Fighter 2, Nights into Dreams, and Sakura Wars are the killer apps for the Sega Saturn. Euro 96 and Sega Rally Championship are major system-sellers for the Sega Saturn in the United Kingdom, with the latter becoming the fastest selling CD game. Dragon Ball Z: Legends served as a killer app for the Sega Saturn in Portugal. Die Hard Arcade and Fighters Megamix boosted the Sega Saturn's sales in the United States. Ridge Racer, Tekken, Wipeout, Tomb Raider, and Crash Bandicoot are the killer apps for the PlayStation. Tomb Raider was released for the Sega Saturn first and for MS-DOS at the same time, but the games contributed substantially to the original PlayStation's early success. Final Fantasy VII is another killer app for the PlayStation. Computing Japan magazine said that it was largely responsible for the PlayStation's global installed base increasing 60% from 10 million units sold by November 1996 to 16 million units sold by May 1997. Super Mario 64 and GoldenEye 007 are the killer apps for the Nintendo 64. Virtua Fighter 3, Sonic Adventure, and The House of the Dead 2 are the killer apps for the Dreamcast. NFL 2K is a killer app for the Dreamcast in the United States.
While it was decorated for valor in the conflict, it also triggered the only episode of open rebellion on the Italian front, in June 1917. The cause was the order to return to the trenches despite the fact that the soldiers had just been sent to the rear to rest. Many soldiers from the 142nd Regiment revolted against the officers, killing three of them along with four carabinieri. After quelling the rebellion with the help of cavalry, mobile artillery and carabinieri, the General Staff decided to punish the Brigade, as a warning against other uprisings: 28 soldiers were shot, while the survivors were sent back to the front under armed escort. The Duke investigated the causes of the rebellion while serving on the Karst Plateau. He blamed the unequal treatment versus other brigades, which enjoyed easier rest shifts. The report of General Tettoni, commander of VII Army Corps, instead blamed it on socialist propaganda and newspaper reports of the Czar's defeat in Russia. The mostly peasant soldiers had been promised an allocation of land derived from large estates after the war. The lack of political will in the implementation of this promise, together with nationalistic tensions due to the Fiume and Dalmatian question, generated a climate of resentment and social unrest, which turned into strikes, anti-government demonstrations and occupations of uncultivated land by the peasants, who organized in leagues or federations of different political colorings.
Sources: en.wikipedia.org
Alice in Chains released their debut album, Facelift, in August 1990 through Columbia Records. Inspired by the music of Black Sabbath, Deep Purple, and Motörhead, the album was initially unsuccessful; the band's first live performances were local shows and festivals around Seattle. Their first tour came as a supporting act to Extreme for a month. Extreme themselves had yet to reach fame and were playing their first tour; neither band drew well. Alice in Chains followed with an opening slot on a tour with Iggy Pop in November 1990, but the band was similarly received with indifference. Their fortunes began to turn when the video for their breakout single, "Man in the Box", landed regular rotation on MTV, beating Blue Murder for a slot on the channel's "Buzz Bin". With newfound momentum, the group secured two supporting slots on two high-profile tours: first, they were selected to join thrash metal bands Anthrax, Megadeth, and Slayer, on the Clash of the Titans Tour in mid-1991, having replaced opening act Death Angel after the band was involved in a bus accident that left its drummer Andy Galeon critically injured and unable to perform. They were then appointed to a slot on Van Halen's For Unlawful Carnal Knowledge Tour later that year; Van Halen frontman Sammy Hagar personally selected the band. Sales of Facelift increased drastically, and by September 1991, it had been certified gold by the Recording Industry Association of America (RIAA).
=== Further reading === Resnick D, Niwayama G (January 1983). "Entheses and enthesopathy. Anatomical, pathological, and radiological correlation". Radiology. 146 (1): 1–9. doi:10.1148/radiology.146.1.6849029. PMID 6849029.
The polar, uncharged amino acids serine (Ser, S), threonine (Thr, T), asparagine (Asn, N) and glutamine (Gln, Q) readily form hydrogen bonds with water and other amino acids. They do not ionize in normal conditions, a prominent exception being the catalytic serine in serine proteases. This is an example of severe perturbation, and is not characteristic of serine residues in general. Threonine has two chiral centers, not only the L (2S) chiral center at the α-carbon shared by all amino acids apart from achiral glycine, but also (3R) at the β-carbon. The full stereochemical specification is (2S,3R)-L-threonine. Because of the presence of phenolic hydroxyl group with a pKa = ~10, tyrosine is best classified as a neutral polar amino acid, but with amphipathic character that makes it less polar than classical small polar amino acid residues. Nonpolar amino acid interactions are the primary driving force behind the processes that fold proteins into their functional three dimensional structures. None of these amino acids' side chains ionize easily, and therefore do not have pKas.
The entries in BTO are updated bi-annually as part of the major update of BRENDA. It is available via the BRENDA website in the category “Ontology Explorer”. The enzyme source terms can be searched via the BTO query form. As a result, the user receives a list of EC numbers which are directly connected to the enzyme information of BRENDA. It is also possible to search via the BRENDA “Source Tissue” search form (“Classic View”). The result page displays all enzymes which are isolated or detected in the searched tissue term, directly linked to BTO. BTO and BRENDA are freely accessible for academic users. It can be freely downloaded via the “Ontology Explorer” of the BRENDA website or in the OBO format from “Obofoundry”. BTO (BRENDA Tissue Ontology) BRENDA Ontology Explorer BRENDA-website ExplorEnz – Enzyme Nomenclature Obofoundry Gene Ontology Consortium EBI-EMBL Bioportal des National Center for Biomedical Ontology, Stanford, USA
The Copenhagen physicists then started a campaign to re-award priority for element 71 to Welsbach and replace the name lutetium with cassiopeium, writing to Welsbach in 1923 of their intentions. This campaign encountered success in the physics literature, but in spite of strong German and Scandinavian support for cassiopeium, lutetium remained embedded in most of the chemical literature, with the International Commission on Atomic Weights in 1930 accepting that element 72 was hafnium but using lutetium for element 71. In 1949, it was decided by the International Union of Pure and Applied Chemistry to recommend the name lutetium, since cassiopeium by then was only used in German and sometimes Dutch, and it was a difficult name to adapt to other languages. It was nonetheless clarified that this was not intended as a statement on priority. Urbain's spelling lutecium was changed to lutetium, in order to derive the name from Latin Lutetia instead of French Lutèce. Pure lutetium metal was first produced in 1953.
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 given either as a once-weekly subcutaneous injection or as an oral tablet taken once daily. The two forms use different absorption strategies, so they are not interchangeable on a milligram-for-milligram basis.