deamidation comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2025-12-04. Where a claim depends on a specific study, the study is described rather than over-claimed.
Pharmacological activity arises from agonism at the glucagon-like peptide-1 receptor, a G protein-coupled receptor expressed in the pancreas, the gastrointestinal tract, and the brainstem. Receptor activation raises intracellular cyclic adenosine monophosphate and enhances insulin release in a glucose-dependent manner, an effect that diminishes when blood glucose concentration is low. Other effects include slowed gastric emptying and hypothalamic satiety signalling. These pathways are described well. Receptor desensitisation rates across tissues, relative to the endogenous hormone, are still under investigation, and reported findings differ between laboratories.
The company that developed the compound filed it as a long-acting analogue, and it gained first approval in 2017 for type 2 diabetes. Later authorisations from several regulators extended the indication to chronic weight management, and the World Health Organization added the glucagon-like peptide-1 receptor agonist drug class to its model list of essential medicines in 2023. Production uses solid-phase peptide synthesis followed by side-chain conjugation and chromatographic purification. Supply constraints and cost differences across regions are well documented. Literature on long-term outcomes continues to grow, with many trials reporting surrogate endpoints rather than hard clinical endpoints.
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.
Storage guidance for the finished injectable product distinguishes the unused state from the in-use state. Before first use, pens are kept refrigerated between 2 and 8 degrees Celsius, protected from light, and never frozen, since freezing can disrupt the peptide or the device. After first use, label instructions in several markets permit storage at room temperature up to about 30 degrees Celsius for a limited number of days. Solid research-grade material is normally held at or below minus 20 degrees Celsius, often with desiccant, and allowed to equilibrate before opening.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular class | 31-amino-acid peptide | Modified glucagon-like peptide-1 analogue |
| Molecular mass | approximately 4114 Da | Calculated for the free peptide backbone |
| Appearance | white to off-white powder | Typical of purified lyophilised peptide batches |
| Solubility class | freely soluble in water | Aqueous solubility improves at slightly alkaline pH |
| Typical storage | -20 degrees Celsius, dry, dark | Protect from repeated freeze-thaw cycles |
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released by intestinal L cells after food intake. The natural hormone acts on pancreatic and central receptors but is degraded within minutes by dipeptidyl peptidase-4 and other peptidases. Semaglutide belongs to the class of long-acting GLP-1 receptor agonists, a group distinguished by structural changes that slow breakdown and extend circulation time. Its development followed earlier short-acting analogues and reflects a general strategy in peptide drug design: preserve receptor activity while blocking proteolytic clearance.
Certificate of analysis documents from suppliers typically report purity by chromatographic area, water content, and counter-ion identity. Independent verification is advisable because reported values can be generated under differing conditions. Impurity profiles matter for research use, where aggregates, deamidation products, and residual solvents may influence experimental results. Container, lot, and chain-of-custody records support traceability. Analytical results are method-dependent, so comparisons between laboratories require the same procedure and reference standards.
Lyophilized peptide material is typically stored at or below -20 °C, with -80 °C used for longer-term archives. Vials should remain sealed and desiccated because moisture promotes aggregation and hydrolysis. Repeated freeze-thaw cycles are avoided since they can alter peptide conformation and reduce recovery. Once reconstituted, solutions are generally kept at 2-8 °C and used within a defined window. Stability beyond those windows depends on buffer composition and concentration, and exact limits are product-specific rather than universal.
Identity and purity are assessed with reversed-phase high-performance liquid chromatography, which separates the peptide from related impurities by hydrophobicity. Mass spectrometry confirms molecular weight and detects truncation or modification products. Peptide mapping after enzymatic digestion verifies the amino acid sequence. Quantitation is often performed by LC-MS/MS or by immunoassay, and the two approaches can give different values because they measure different things. Method validation parameters such as accuracy, precision, and limit of quantitation are reported alongside results.
Bowfin eggs are adhesive, and attach to aquatic vegetation, roots, gravel, and sand. After hatching, larval bowfin do not swim actively in search of food. During the 7-9 days required for yolk-sac absorption, they attach to vegetation by means of an adhesive organ on their snout, and remain protected by the parent male bowfin. Bowfin aggressively protect their spawn from the first day of incubation to a month or so after the eggs have hatched. When the fry are able to swim and forage on their own, they form a school and leave the nest accompanied by the parent male bowfin, which slowly circles them to prevent separation. Bowfin reach sexually maturity at 2-3 years of age. They can live up to 30 years in captivity.
=== February === 1 February A ban on owning an American XL Bully dog comes into force in England and Wales. It is now a criminal offence to own one of the dogs unless the owner has successfully applied for the dog to be exempt. The Bank of England holds interest rates at 5.25%. Climate activist Greta Thunberg appears at Westminster Magistrates' Court, charged with breaching section 14 of the Public Order Act 1986. Her case, and that of four co-defendants, is thrown out the following day. COVID-19 vaccination in the United Kingdom: The first private service for COVID-19 vaccination begins rolling out to pharmacies around the UK, allowing those who are under 65 to receive the latest booster. 2 February Senior Labour MP Darren Jones confirms that the party has ditched its commitment to spend £28bn a year on green investment schemes if it wins the next general election. The killers of 16-year-old transgender girl Brianna Ghey are named as Scarlett Jenkinson and Eddie Ratcliffe, both aged 15 at the time of the murder in February 2023. They are sentenced at Manchester Crown Court to minimum terms of 22 and 20 years, respectively. Water UK, the umbrella trade organisation for the UK's water companies, says that the average annual water bill is expected to increase by 6% in England and Wales from April, an average rise of £27 to £473. 3 February 2024 Northern Ireland Executive formation: The Northern Ireland Assembly meets to elect a new Speaker. Edwin Poots, a former leader of the DUP, is chosen to be the Assembly's 7th Speaker.
=== Restrictive lung diseases === Some types of chronic lung diseases are classified as restrictive lung disease, because of a restriction in the amount of lung tissue involved in respiration. These include pulmonary fibrosis which can occur when the lung is inflamed for a long period of time. Fibrosis in the lung replaces functioning lung tissue with fibrous connective tissue. This can be due to a large variety of occupational lung diseases such as Coalworker's pneumoconiosis, autoimmune diseases or more rarely to a reaction to medication. Severe respiratory disorders, where spontaneous breathing is not enough to maintain life, may need the use of mechanical ventilation to ensure an adequate supply of air.
Sources: en.wikipedia.org
During his stay in Shanghai, Lula criticized US dollar dominance stating "Who was it that decided that the dollar was the currency after the disappearance of the gold standard?" and "why can't we do trade based on our own currencies?". He also urged developing nations to find an alternative currency to the dollar. On 14 April, Lula separately met with Congress chairman Zhao Leji, Chinese premier Li Qiang and Chinese leader Xi Jinping in Beijing and signed numerous agreements (worth BRL 50 billion – nearly US$10.1 billion) aiming at mutual cooperation such as to further develop the CBERS-4 constellation, to create a pannel to follow the Sustainable Development Goals in both countries and to open a Sino-Brazilian trade fair mainly focused on green, low-carbon economy and digitalization, among other agreements. China and Brazil also urged developed countries to speed up climate change mitigation funds following the rich countries' commitment at the COP 15 to donate US$100 billion a year to do so from 2009 on. In July 2024, Brazil and China signed an agreement to extend tourist and business visas validity from 5 to 10-years long. In July 2024, Vice-President Geraldo Alckmin visited China amid the celebrations of bicentenary of the establishment of the Brazilian-Chinese relations, and also reportedly as a preparation for Brazil to join the Chinese Belt and Road Initiative. During the visit Chinese leader Xi Jinping praised Sino-Brazilian relations as a "friendship" that "goes far beyond the bilateral relations".
== Other uses == Chart Rulership or Chart Ruler, in astrology Comfort room, another name for a public toilet Consciousness raising, in social activism Continuing resolution, a type of appropriations legislation in the US Councillor, a title for a public servant, used in Australia and New Zealand Cree language (ISO 639 alpha-2 code CR) Critical reading, a skill measured by the Scholastic Aptitude Test (SAT) Crore, a number representing 10,000,000 in the Hindu-Arabic numeral system Cr$ or ₢, symbol for Brazilian cruzeiro
Henri Poincaré laid the seeds for the discovery of radioactivity through his interest in and studies of X-rays, which significantly influenced physicist Henri Becquerel. Radioactivity was discovered in 1896 by Becquerel while working with phosphorescent materials. These materials glow in the dark after exposure to light, and Becquerel suspected that the glow produced in cathode-ray tubes by X-rays might be associated with phosphorescence. He wrapped a photographic plate in black paper and placed various phosphorescent salts on it. All results were negative until he used uranium salts. The uranium salts caused a blackening of the plate in spite of the plate being wrapped in black paper. In 1897, Marie Curie began studying the radiation emitted by uranium compounds. Curie named the radiation rayons de Becquerel, "Becquerel Rays" and showed that these rays were a property of atoms. While X-rays were produced using electrical energy, the source of energy for radiation was a mystery. In 1899, Julius Elster and Hans Geitel performed key experiments to find the energy source for radioactivity, excluding extraction of energy from air by measurements in a vacuum and extraction of energy from outer space by measurements 300m down a mine in the Harz mountains. If the atoms themselves were the source of energy, this meant the seemingly immutable atoms must be altered when emitting the rays. In 1900 Curie summarized the puzzle of radioactivity as a choice between two equally unlikely possibilities: either energy was not conserved or chemical elements could be transmuted.
Industrial production of ethoxylates is realized by a direct reaction of higher alcohols, acids, or amines with ethylene oxide in the presence of an alkaline catalyst at a temperature of 120–180 °C (250–360 °F). Modern plants producing ethoxylates are usually based on the BUSS LOOP reactors technology, which is based on a three-stage continuous process. In the first stage, the initiator or catalyst of the reaction and the feedstock are fed into the container, where they are mixed, heated, and vacuum dried. Then reaction is carried out in a special insulated reactor in an inert atmosphere (nitrogen) to prevent a possible explosion of ethylene oxide. Finally, the reaction mixture is neutralized, degassed, and purified.
Sources: en.wikipedia.org
=== Medications === Pentoxifylline is a useful add-on treatment to compression stockings and may also help by itself. It works by reducing platelet aggregation and thrombus formation. Gastrointestinal disturbances were reported as a potential adverse effect. Sulodexide, which reduces the formation of blood clots and reduces inflammation, may improve the healing of venous ulcers when taken in conjunction with proper local wound care. Further research is necessary to determine potential adverse effects, the effectiveness, and the dosing protocol for sulodexide treatment. An oral dose of aspirin is being investigated as a potential treatment option for people with venous ulcers. A 2016 Cochrane systematic review concluded that further research is necessary before this treatment option can be confirmed to be safe and effective. Oral zinc supplements have not been proven to be effective in aiding the healing of venous ulcers; however, more research is necessary to confirm these results. Treatments aimed at decreasing protease activity to promote healing in chronic wounds have been suggested; however, the benefit remains uncertain. There is also a lack of evidence on the effectiveness of testing for elevated proteases in venous ulcers and treating them with protease-modulating treatment. There is low certainty evidence that protease modulating matrix treatment is helpful in the healing of venous ulcers. Flavonoids may be useful for treating venous ulcers, but the evidence must be interpreted cautiously.
=== 2014: Merger with Burger King === On August 24, 2014, American fast-food chain Burger King announced that it was in negotiations to merge with Tim Hortons Inc.; the proposed $18 billion mergers would involve a tax inversion into Canada, with a new holding company majority-owned by 3G Capital, and the remaining shares in the company held by current Burger King and Tim Hortons shareholders. A Tim Hortons representative stated that the proposed merger would allow Tim Hortons to leverage Burger King's resources for international growth; the two chains would retain separate operations post-merger. News of the proposal caused Tim Hortons' shares to increase in value by 28 percent. On August 25, 2014, Burger King officially confirmed its intent to acquire Tim Hortons Inc. in a deal totaling CA$12.5 billion (US$11.4 billion). 3G Capital offered to purchase the company at $65.50 per share, with existing shareholders receiving $65.50 in cash and 0.8025 shares in the new holding company: per-share—all-cash ($88.50) and all-shares (3.0879) options were also made available. The agreement planned to result in 3G Capital (which held a 71% majority stake in Burger King) holding a 51% majority stake in the new company, Tim Hortons' existing shareholders owning 22%, and Burger King's owning 27% with the new entity based in Oakville and listed on both the TSX and New York Stock Exchange.
== Roasters == The sudden influx of coffee shops have replaced the once traditional "dabang" which were common meetings places serving a selection of customary teas. In addition to large US chains that have profited from the surge in demand for coffee, local businesses and entrepreneurs have also seized the opportunities. As of 2014 South Korea boasted 17,000 coffee shops and the capital, Seoul, had more outlets of Starbucks than any other city in the world, even New York.
=== Parts === The head of the pancreas sits within the curvature of the duodenum and wraps around the superior mesenteric artery and vein. To the right sits the descending part of the duodenum, and between these travel the superior and inferior pancreaticoduodenal arteries. Behind rest the inferior vena cava and the common bile duct. In front sit the peritoneal membrane and the transverse colon. A small uncinate process emerges from below the head, situated behind the superior mesenteric vein and sometimes artery. A pancreatic notch is a separation between the neck of the pancreas and the uncinate process. The neck of the pancreas separates the head of the pancreas, located in the curvature of the duodenum, from the body. The neck is about 2 cm (0.79 in) wide and sits in front of where the portal vein is formed. The neck lies mostly behind the pylorus of the stomach and is covered with peritoneum. The anterior superior pancreaticoduodenal artery travels in front of the neck of the pancreas. The body of the pancreas is the largest part of the pancreas and mostly lies behind the stomach, tapering along its length. The peritoneum sits on top of the body of the pancreas, and the transverse colon in front of the peritoneum. Behind the pancreas are several blood vessels, including the aorta, the splenic vein, and the left renal vein, as well as the beginning of the superior mesenteric artery.
=== Mammalian === Mammalian tyrosinase is a single membrane-spanning transmembrane protein. In humans, tyrosinase is sorted into melanosomes and the catalytically active domain of the protein resides within melanosomes. Only a small, enzymatically inessential part of the protein extends into the cytoplasm of the melanocyte. As opposed to fungal tyrosinase, human tyrosinase is a membrane-bound glycoprotein and has 13% carbohydrate content. The derived TYR allele (rs2733832) is associated with lighter skin pigmentation in human populations. It is most common in Europe, but is also found at lower, moderate frequencies in Central Asia, the Middle East, North Africa, and among the San and Mbuti Pygmies.
Sources: en.wikipedia.org
It is a glucagon-like peptide-1 receptor agonist, often grouped with the incretin mimetics. Its backbone is modified from the human hormone to resist enzymatic degradation and to bind albumin. These two features distinguish it from the native peptide.
No. It shares high sequence identity but carries non-natural modifications that alter its stability and clearance. The naturally occurring hormone is broken down within minutes, while the synthetic analogue circulates far longer.
Attachment to serum albumin reduces renal filtration of the peptide and shields it from enzymatic breakdown. The consequence is a much longer interval between administrations than unmodified peptides allow. The precise contribution of binding affinity to overall duration is still being quantified.
Ice formation concentrates solutes and can mechanically stress the peptide or damage the delivery device. Thawing afterwards may leave aggregates that are not visible to the eye. Refrigeration keeps the solution above its freezing point while slowing chemical degradation.