The short version of deamidation fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2025-10-06. Anything still debated is marked as such rather than presented as settled.
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.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white solid | typical of a lyophilised peptide preparation |
| Solubility behaviour | pH dependent | lowest near the isoelectric point |
| Storage of bulk material | Minus 20 degrees Celsius or below | protect from light and moisture |
| Storage of unused pen | 2 to 8 degrees Celsius | do not freeze |
| Common assay method | Reversed-phase HPLC | identity, purity and content |
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
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.
Semaglutide is a synthetic peptide of thirty-one amino acids that shares roughly ninety-four percent sequence identity with human glucagon-like peptide-1. Two substitutions resist enzymatic cleavage by dipeptidyl peptidase-4, and a fatty diacid side chain attached through a linker promotes binding to serum albumin. That albumin binding slows renal clearance and extends the circulating half-life from minutes to approximately one week. The structural changes are well established in the published literature. Whether the same modifications affect receptor signalling bias in ways that matter clinically remains an open question.
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.
Solid peptide material is generally kept at reduced temperature to limit degradation. Short-term storage at 2 to 8 degrees Celsius is common, while longer archival storage at minus 20 degrees Celsius or below is typical for lyophilised powder. Vials should remain sealed and protected from light, because ultraviolet exposure can oxidise susceptible residues. Repeated freeze-thaw cycles are avoided, as they promote aggregation and loss of soluble material. Solutions are less stable than solids and are usually prepared close to the time of use.
=== Flagship facility === UPMC Presbyterian Shadyside is UPMC's primary flagship medical entity and represents the core of UPMC's academic, teaching, trauma, specialty and research-related facilities, serving as the system's primary academic hub and Pennsylvania's largest inpatient acute care hospital. UPMC Presbyterian Shadyside includes UPMC Presbyterian hospital and the physically conjoined UPMC Eye & Ear and UPMC Montefiore hospitals as well as the UPMC Western Psychiatric Hospital that also serves as the University of Pittsburgh's Thomas Detre Hall. These facilities are all located on the western side of the University of Pittsburgh's main campus in the Oakland neighborhood of Pittsburgh. The hospitals are also physically connected to the University of Pittsburgh School of Medicine's Scaife Hall, the University of Pittsburgh School of Nursing's Victoria Hall, Falk Clinic, three of the university's biomedical science towers, and the university's Lothrop Hall dormitory, all of which are surrounded by a variety of other academic facilities. UPMC Presbyterian Shadyside also encompasses the UPMC Shadyside hospital campus which includes the University of Pittsburgh Cancer Institute in the UPMC Hillman Cancer Center which are located near the university's Centre Plaza Apartments student housing. The UPMC Shadyside facilities are located in the adjacent neighborhood of Shadyside approximately 1.5 miles (2.4 km) from the Oakland-based hospitals and are connected by regular shuttle service.
==== Lasso peptides ==== Lasso peptide biosynthesis requires at least three genes, referred to as the A, B, and C proteins. The A gene encodes the precursor peptide, which is modified by the B and C proteins into the mature natural product. The B protein is an adenosine triphosphate-dependent cysteine protease that cleaves the leader region from the precursor peptide. The C protein displays homology to asparagine synthetase and is thought to activate the carboxylic acid side chain of a glutamate or aspartate residue via adenylylation. The N-terminal amine formed by the B protein (protease) then reacts with this activated side chain to form the macrocycle-forming isopeptide bond. The exact steps and reaction intermediates in lasso peptide biosynthesis remain unknown due to experimental difficulties associated with the proteins. Commonly, the B protein is referred to as the lasso protease, and the C protein is referred to as the lasso cyclase. Some lasso peptide biosynthetic gene clusters also require an additional protein of unknown function for biosynthesis. Additionally, lasso peptide gene clusters usually include an ABC transporter (D protein) or an isopeptidase, although these are not strictly required for lasso peptide biosynthesis and are sometimes absent. No X-ray crystal structure is yet known for any lasso peptide biosynthetic protein. The biosynthesis of lasso peptides is particularly interesting due to the inaccessibility of the threaded-lasso topology to chemical peptide synthesis.
=== Regulation in Britain and the United States === Before the 1920s, regulation in Britain was controlled by pharmacists. Pharmacists who were found to have prescribed opium for illegitimate uses and anyone found to have sold opium without proper qualifications would be prosecuted. With the passing of the Rolleston Act in Britain in 1926, doctors were allowed to prescribe opiates such as morphine and heroin if they believed their patients demonstrated a medical need. Because addiction was viewed as a medical problem rather than an indulgence, doctors were permitted to allow patients to wean themselves off opiates rather than cutting off any opiate use altogether. The passing of the Rolleston Act put the control of opium use in the hands of medical doctors instead of pharmacists. Later in the 20th century, addiction to opiates, especially heroin in young people, continued to rise and so the sale and prescription of opiates was limited to doctors in treatment centres. If these doctors were found to be prescribing opiates without just cause, then they could lose their licence to practice or prescribe drugs. Abuse of opium in the United States began in the late 19th century and was largely associated with Chinese immigrants. During this time the use of opium had little stigma; the drug was used freely until 1882 when a law was passed to confine opium smoking to specific dens. Until the full ban on opium-based products came into effect just after the beginning of the twentieth century, physicians in the US considered opium a miracle drug that could help with many ailments.
In late 1807, Spanish and Napoleonic forces threatened the security of continental Portugal, causing Prince Regent John, in the name of Queen Maria I, to move the royal court from Lisbon to Rio de Janeiro. There they established some of Brazil's first financial institutions, such as its local stock exchanges and its National Bank, additionally ending the Portuguese monopoly on Brazilian trade and opening Brazil's ports to other nations. In 1809, in retaliation for being forced into exile, the Prince Regent ordered the conquest of French Guiana. With the end of the Peninsular War in 1814, the courts of Europe demanded that Queen Maria I and Prince Regent John return to Portugal, deeming it unfit for the head of an ancient European monarchy to reside in a colony. In 1815, to justify continuing to live in Brazil, where the royal court had thrived for six years, the Crown established the United Kingdom of Portugal, Brazil and the Algarves, thus creating a pluricontinental transatlantic monarchic state. However, the leadership in Portugal, resentful of the new status of its larger colony, continued to demand the return of the court to Lisbon (see Liberal Revolution of 1820). In 1821, acceding to the demands of revolutionaries who had taken the city of Porto, John VI departed for Lisbon. There he swore an oath to the new constitution, leaving his son, Prince Pedro de Alcântara, as Regent of the Kingdom of Brazil.
Sources: en.wikipedia.org
=== Development === Insecticides with systemic activity against sucking pests, which are safe to pollinators, are sought after, particularly in view of the partial bans on neonicotinoids. Revised 2023 guidance by registration authorities describes the bee testing that is required for new insecticides to be approved for commercial use.
== Changes for 2020 exam == The Central Board of Secondary Education (CBSE) has been conducting two separate Mathematics examinations in the class 10 board examination, starting from the 2020 session. Mathematics exam till 2019 was Mathematics (Standard), and an easier version, Mathematics (Basic), has been introduced. The option to choose mathematics is available on the registration form for the Class 10 CBSE board examination. Candidates are required to select their test choice while filling out the registration form for the CBSE Class 10 board examination 2020. Minister of Education, MoE (previously Minister of Human Resource Department, HRD), amid the coronavirus outbreak had ordered rescheduling of pending examinations. The exams rescheduled were to be conducted between 1 and 15 July. On 26 June, CBSE released as circular which cancelled the remaining exams and give scores based on the scores of the exams already taken by students. Some students of Delhi who were able to provide three or fewer exams were scored as per their performance in internal exams. This decision came after a judicial ruling.
=== Blood tests === When RA is clinically suspected, a physician may test for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs measured as anti-CCP antibodies). The test is positive approximately two-thirds of the time, but a negative RF or CCP antibody does not rule out RA; rather, the arthritis is called seronegative, which occurs in approximately a third of people with RA. During the first year of illness, rheumatoid factor is more likely to be negative with some individuals becoming seropositive over time. RF is a non-specific antibody and seen in about 10% of healthy people, in many other chronic infections like hepatitis C, and chronic autoimmune diseases such as Sjögren's disease and systemic lupus erythematosus. Therefore, the test is not specific for RA. Hence, new serological tests check for anti-citrullinated protein antibodies ACPAs. These tests are again positive in 61–75% of all RA cases, but with a specificity of around 95%. As with RF, ACPAs are many times present before symptoms have started. The by far most common clinical test for ACPAs is the anti-cyclic citrullinated peptide (anti CCP) ELISA. In 2008, a serological point-of-care test for the early detection of RA combined the detection of RF and anti-MCV with a sensitivity of 72% and specificity of 99.7%. To improve the diagnostic capture rate in the early detection of patients with RA and to risk-stratify these individuals, the rheumatology field continues to seek complementary markers to both RF and anti-CCP.
=== Temperature === Conversion of both CO and CO2 to CH4 starts at a catalyst temperature below 300°C, but the conversion is incomplete and peak tailing is evident. At around 340°C, conversion is complete, as indicated by area measurements, but some tailing limits the peak height. At 360-380°C, tailing is eliminated and there is little change in peak height up to 400°C. Operating temperatures for various methanizers range from 350-400°C. Although carbonization of CO has been reported at temperatures above 350°, it is rather a rare phenomenon.
At high pressures, above approximately 10 GPa and temperatures of a few hundred kelvin or less, α-iron changes into another hexagonal close-packed (hcp) structure, which is also known as ε-iron. The higher-temperature γ-phase also changes into ε-iron, but does so at higher pressure. The physical properties of iron at very high pressures and temperatures have been studied extensively because of their relevance to theories about the cores of the Earth and other planets. The Earth's inner core is generally presumed to consist of an iron-nickel alloy with ε (or β) structure. Some controversial experimental evidence exists for a stable β phase at pressures above 50 GPa and temperatures of at least 1500 K. It is supposed to have an orthorhombic or a double hcp structure. (Confusingly, the term "β-iron" is sometimes also used to refer to α-iron above its Curie point, when it changes from being ferromagnetic to paramagnetic, even though its crystal structure has not changed.)
Sources: en.wikipedia.org
Automated coagulation machines or Coagulometers measure the ability of blood to clot by performing any of several types of tests including Partial thromboplastin times, Prothrombin times (and the calculated INRs commonly used for therapeutic evaluation), Lupus anticoagulant screens, D dimer assays, and factor assays. Coagulometers require blood samples that have been drawn in tubes containing sodium citrate as an anticoagulant. These are used because the mechanism behind the anticoagulant effect of sodium citrate is reversible. Depending on the test, different substances can be added to the blood plasma to trigger a clotting reaction. The progress of clotting may be monitored optically by measuring the absorbance of a particular wavelength of light by the sample and how it changes over time.
== Association football scandals == 1915 British football match-fixing scandal 1964 British football match-fixing scandal Bundesliga scandal (1965) 1971 Bundesliga scandal 1980 Italian football scandal – a match fixing scandal in Italian football involving several major teams. 1986 Totonero 1988 Mexico national football team scandal 1989 Maracanazo of the Chilean team 1993 French football bribery scandal – a match fixing scandal involving a 1992–93 French Division 1 match between Olympique de Marseille and Valenciennes, in which Valenciennes players were bribed by Olympique de Marseille president Bernard Tapie, through Marseille midfielder Jean-Jacques Eydelie. It is believed that Eydelie offered three Valenciennes players (Jorge Burruchaga, Christophe Robert and Jacques Glassman) ₣250,000 to "take the foot off of the gas" in a May 20 match between the sides, so that the team would be fresh to play in the Champions League final soon after. Marseille were subsequently stripped off the 1992–93 French Division 1 title, relegated to Division 2 and handed bans from all 1993 UEFA competitions. The French Football Federation also suspended Eydelie, Robert and Burruchaga, whilst Tapie was replaced as club president by Bernard Moreau. Tapie received a prison sentence of over two years, of which he served six months and received a ₣20,000 fine, whilst Eydelie, Robert, Burruchaga and Marseille general manager Jean-Pierre Bernès were all given prison sentences and fined. Eydelie's prison sentence was a suspended sentence.
On March 23 2023, Brazilian police raided the Salgueiro favela in São Gonçalo, Rio de Janeiro, killing Leonardo Costa Araujo, the head of CV in Para, and other 12 gangsters. On September 4 2025, eight members of the Terceiro Comando Puro were killed in a shootout with police in Rio de Janeiro. Later, on October 28, 2025, against the backdrop of COP30, Brazilian police launched Operation Containment on Comando Vermelho spots in Rio de Janeiro, arresting at least 81 suspected gang members while resulting in the deaths of more than 132 people, including four police officers and at least 17 residents without prior criminal records. On 14 January 2026, four people were killed in a police operation against the Comando Vermelho in the Salgueiro favela of Rio de Janeiro. On 18 March, eight people, including Comando Vermelho commander Claudio Augusto dos Santos, were killed in police raids across Rio de Janeiro.
== History == Antibody Solutions was founded in 1995 by current president, John Kenney, PhD, Judith Lynch-Kenney, and Dennis and Bette Gould. Dr. Kenney previously managed the monoclonal antibody (MAb) development laboratory for Syntex Research (Roche) in Palo Alto, while Gould managed the MAb production facility for Syva Diagnostics. Gould left Antibody Solutions in 1997, eventually becoming a vice president for Sepragen Corporation. Kenney and Gould were assisted in the startup of the company by Barry Bredt, who had the foresight to acquire the domain name, www.antibody.com, for the company. Bredt later became director of the University of California at San Francisco’s General Clinical Research Center, and was a pioneer of the HIV/AIDS Diagnostics EasyCD4; he died on April 8, 2007. Antibody Solutions was incorporated in 1998 with Dr. Kenney as president and Judith Lynch-Kenney as chief financial officer. One of the first independent antibody discovery companies, the firm focused on custom antibody discovery for therapeutics, diagnostics and critical reagents. The company pioneered the use of bioreactors in antibody research by becoming the first CRO to produce antibodies in CELLine flasks in 2000. From 2004 to 2011, Antibody Solutions was headquartered in Mountain View, a short distance from Shoreline Park, Moffett Field and the Googleplex. In 2011, the company moved to new facilities in Sunnyvale. It moved to its current 33,300-square-foot location at 3033 Scott Blvd. in Santa Clara near the San Tomas Expressway in mid-2019. A grand opening for the Scott Blvd.
The collagenases are capable of degrading triple-helical fibrillar collagens into distinctive 3/4 and 1/4 fragments. These collagens are the major components of bone, cartilage and dentin, and MMPs are the only known mammalian enzymes capable of degrading them. The collagenases are No. 1, No. 8, No. 13, and No. 18. In addition, No. 14 has also been shown to cleave fibrillar collagen, and there is evidence that No. 2 is capable of collagenolysis. In MeSH, the current list of collagenases includes No. 1, No. 2, No. 8, No. 9, and No. 13. Collagenase No. 14 is present in MeSH but not listed as a collagenase, while No. 18 is absent from MeSH. The main substrates of the gelatinases are type IV collagen and gelatin, and these enzymes are distinguished by the presence of an additional domain inserted into the catalytic domain. This gelatin-binding region is positioned immediately before the zinc-binding motif, and forms a separate folding unit that does not disrupt the structure of the catalytic domain. The gelatinases are No. 2 and No. 9. The stromelysins display a broad ability to cleave extracellular matrix proteins but are unable to cleave the triple-helical fibrillar collagens. The three canonical members of this group are No. 3, No. 10, and No. 11. All six membrane-type MMPs (No. 14, No. 15, No. 16, No. 17, No. 24, and No. 25) have a furin cleavage site in the pro-peptide, which is a feature also shared by No. 11.
Sources: en.wikipedia.org
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.
Size-exclusion chromatography is the most common technique, separating monomer from dimer and higher-order species by hydrodynamic volume. It is usually paired with ultraviolet detection and, for trace work, with multi-angle light scattering. Results depend on mobile-phase conditions, so method details matter when comparing datasets.
The detailed degradation profile under real-world temperature excursions and repeated handling is not fully described in the open literature. Relative contributions of photo-degradation versus thermal pathways are also incompletely mapped. Whether specific impurity species carry different biological activity is an open question rather than an established finding.
It belongs to the incretin mimetic class and acts as a long-acting glucagon-like peptide-1 receptor agonist. The class includes several peptides with different half-lives and routes of administration.