If you have been reading about deamidation and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2025-10-23. Numbers and descriptions here follow the published literature rather than marketing material.
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
Handling guidance for research quantities calls for single-use aliquots, an inert atmosphere where practical, and avoidance of repeated freeze-thaw cycles that accelerate aggregation. Certificates of analysis typically report purity by peak area, water content, counter-ion identity, and residual solvent levels. In the scientific literature the compound is usually described by its full amino acid sequence, its registry number, or its structural class rather than by any proprietary label. Reporting standards vary between journals, and reviewers increasingly request raw chromatograms alongside tabulated purity figures. Whether current purity thresholds are adequate for every experimental context is debated.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Acylated GLP-1 receptor agonist | 31-residue synthetic peptide |
| Molecular formula | C187H291N45O59 | established for the free peptide |
| Appearance | White to off-white powder | as supplied before formulation |
| Solubility | Freely soluble in water | aqueous buffers near neutral pH |
| Typical storage | 2 to 8 degrees Celsius, protected from light | powder and solution forms differ in shelf life |
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.
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.
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.
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.
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.
The substrates of this enzyme are trans-4-(dimethylamino)azobenzene, two equivalents of reduced nicotinamide adenine dinucleotide phosphate (NADPH), and two protons. Its products are aniline, N,N-dimethylphenylenediamine, and oxidised NADP+. This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with NAD+ or NADP+ as acceptor.
The use of MRI is currently contraindicated for patients with pacemakers, cochlear implants, some indwelling medication pumps, certain types of cerebral aneurysm clips, metal fragments in the eyes, some metallic hardware due to the powerful magnetic fields, and strong fluctuating radio signals to which the body is exposed. Areas of potential advancement include functional imaging, cardiovascular MRI, and MRI-guided therapy.
Tetrahydrobiopterin (branded as Kuvan) (sapropterin dihydrochloride), a small molecule drug for phenylketonuria, introduced in 2007 as the first medication-based intervention to treat phenylketonuria Arylsulfatase B (branded as Naglazyme) (galsulfase), a recombinant protein therapeutic for Maroteaux–Lamy syndrome (also called mucopolysaccharidosis type VI) Iduronidase (branded as Aldurazyme), a recombinant protein therapeutic for mucopolysaccharidosis I Amifampridine (branded as Firdapse), a small molecule drug for Lambert–Eaton myasthenic syndrome (as of 2013 approved in the EU only) Elosulfase alfa (branded as Vimizim), is the only enzyme replacement therapy to address the cause of Morquio A Syndrome (MPS IVA), which affects an estimated 3,000 patients in the developed world. The disease occurs as a result of a deficiency of activity in an enzyme involved in glycosaminoglycan (GAG) metabolism. Cerliponase alfa (branded as Brineura), is an enzyme replacement treatment for Batten disease, which is a form of neuronal ceroid lipofuscinosis. It was approved in 2017. Valoctocogene roxaparvovec (branded as Roctavian) is an adeno-associated viral vector for treatment of hemophilia A that aims to transfer a working copy of the Factor VIII gene into patients who lack one. It was approved in the EU in August 2022. Biomarin is working to develop several new drugs.
Turin (Italian: Torino) is a city and a business and cultural centre in northern Italy. It is the capital and largest city of Piedmont and of the Metropolitan City of Turin. From 1861 to 1865, it was the first capital of the Kingdom of Italy. The city is mainly on the western bank of the River Po, below its Susa Valley, and is surrounded by the western Alpine arch and Superga hill. The population of the city proper is 855,654 as of 2026, while the population of the urban area is estimated by Eurostat to be 1.7 million inhabitants. The Turin metropolitan area is estimated by the OECD to have a population of 2.2 million. The city was historically a major European political centre. From 1563, it was the capital of the Duchy of Savoy, then of the Kingdom of Sardinia ruled by the House of Savoy, and then the first capital of the Kingdom of Italy from 1861 to 1865. Turin is sometimes called "the cradle of Italian liberty" for having been the political and intellectual centre of the Risorgimento that led to the unification of Italy, as well as the birthplace of notable individuals who contributed to it, such as Camillo Benso, Count of Cavour. Although much of its political influence had been lost by World War II, it had become a centre of anti-fascist movements during the Ventennio fascista, including the Italian resistance movement. Postwar Turin became a major European crossroads for industry, commerce and trade, and is part of the industrial triangle, along with Milan and Genoa. In 2004 it ranked third in Italy, after Milan and Rome, for economic strength.
== Scientific approach == In xenobiology, the aim is to design and construct biological systems that differ from their natural counterparts on one or more fundamental levels. Ideally these new-to-nature organisms would be different in every possible biochemical aspect exhibiting a very different genetic code. The long-term goal is to construct a cell that would store its genetic information not in DNA but in an alternative informational polymer consisting of xeno nucleic acids (XNA), different base pairs, using non-canonical amino acids and an altered genetic code. So far cells have been constructed that incorporate only one or two of these features.
Sources: en.wikipedia.org
{\displaystyle {\begin{aligned}u(y,z)&={\frac {G}{2\mu \left({\frac {1}{a^{2}}}+{\frac {1}{b^{2}}}\right)}}\left(1-{\frac {y^{2}}{a^{2}}}-{\frac {z^{2}}{b^{2}}}\right),\\[6pt]Q&={\frac {\pi Ga^{3}b^{3}}{4\mu \left(a^{2}+b^{2}\right)}}.\end{aligned}}}
== Publications == Marley, Christopher (September 1, 2008). Pheromone: The Insect Artwork of Christopher Marley. Pomegranate Communications. ISBN 978-0764946196. Marley, Christopher (April 14, 2015). Biophilia. Harry N. Abrams. ISBN 978-1419715617. Marley, Christopher (January 1, 2023). Exquisite Creatures: A Dialogue with Art, Nature, and Science. Christopher Marley Studio. ISBN 979-8986360805.
It is believed that Tazarotene may inhibit melanoma growth through the tazarotene-induced genes (TIG) family (TIG1, TIG2, TIG3) by specifically suppressing the mTOR pathway, inducing endoplasmic reticulum stress, and promoting cell differentiation and apoptosis. It further modulates the tumor microenvironment by enhancing immune surveillance (primarily through TIG2-mediated recruitment of natural killer and T cells) and may reduce pro-tumorigenic inflammatory markers like IL-6. These mechanisms collectively suppress myeloid-derived suppressor cells (MDSC), tumor proliferation, invasion, and metastasis, positioning tazarotene-regulated pathways as potential targets for melanoma immunotherapy.
=== Oil === One estimate for yield of oil from kernels is 250 L/ha (22 imperial gallons per acre). The oil can be used as a food supplement, as a base for cosmetics, and for hair and the skin. Seeds of Moringa can also be used in production of biofuel.
Biography at the Biographical Directory of the United States Congress Financial information (federal office) at the Federal Election Commission Legislation sponsored at the Library of Congress Profile at Vote Smart Campaign contributions at OpenSecrets.org Follow the Money – John Kennedy 2007 2005 2003 1999 Louisiana Treasurer campaign contributions
Sources: en.wikipedia.org
== References == Brendon, Piers (2010). The Decline and Fall of the British Empire, 1781–1997 (1st Vintage books ed.). New York City: Vintage Books. ISBN 9780307388414. Cilliers, Jakkie (1985). Counter-Insurgency in Rhodesia (PDF). Beckenham, United Kingdom: Croom Helm. ISBN 0-7099-3412-2. Cline, Lawrence E. (2005). "Pseudo Operations and Counterinsurgency: Lessons from Other Countries" (PDF). Strategic Studies Institute, US Army War College. Cross, G. (2017). Dirty War: Rhodesia and Chemical Biological Warfare, 1975–1980. Helion & Company. ISBN 978-1-911512-12-7. Dzimbanhete, Jephias Andrew (March 2017). "Reverberations of Rhodesian Propaganda in Narratives of Zimbabwe's Liberation War". Journal of Pan African Studies. 10 (1): 295–307. Evans, Michael (June 2007). "The Wretched of the Empire: Politics, Ideology and Counterinsurgency in Rhodesia, 1965–80". Small Wars & Insurgencies. 18 (2): 175–195. doi:10.1080/09574040701400601. S2CID 144153887. Gatchel, Theodore L. (2008). "Pseudo Operations – A Double Edged Sword of Counterinsurgency". In Norwitz, Jeffery H. (ed.). Armed Groups: Studies in National Security, Counterterrorism, and Counterinsurgency. Newport, Rhode Island: US Naval War College. pp. 61–74. ISBN 9781884733529. Martinez, Ian (December 2002). "The History of the Use of Bacteriological and Chemical Agents during Zimbabwe's Liberation War of 1965–80 by Rhodesian Forces". Third World Quarterly. 23 (6): 1159–1179. doi:10.1080/0143659022000036595. ISSN 0143-6597. JSTOR 3993569. S2CID 145729695. McLaughlin, Peter (August 1991).
=== Other uses === The demand for selenium by the electronics industry is declining. Its photovoltaic and photoconductive properties are still useful in photocopying, photocells, light meters and solar cells. Its use as a photoconductor in plain-paper copiers once was a leading application, but in the 1980s, the photoconductor application declined (although it was still a large end-use) as more and more copiers switched to organic photoconductors. Zinc selenide was the first material for blue LEDs, but gallium nitride dominates that market. Cadmium selenide can be used to make quantum dots. Sheets of amorphous selenium convert X-ray images to patterns of charge in xeroradiography and in solid-state, flat-panel X-ray cameras. Ionized selenium (Se+24, where 24 of the outer D, S and P orbitals are stripped away due to high input energies) is one of the active mediums used in X-ray lasers. 75Se is used as a gamma source in industrial radiography. Selenium catalyzes some chemical reactions, but it is not widely used because of issues with toxicity. In X-ray crystallography, incorporation of one or more selenium atoms in place of sulfur helps with multiple-wavelength anomalous dispersion and single wavelength anomalous dispersion phasing. Selenium is used in the toning of photographic prints, and it is sold as a toner by numerous photographic manufacturers. Selenium intensifies and extends the tonal range of black-and-white photographic images and improves the permanence of prints.
=== Multiple sclerosis symptoms === Spasticity. Based on the results of three high-quality trials and five of lower quality, oral cannabis extract was rated as effective, and THC as probably effective, for improving people's subjective experience of spasticity. Oral cannabis extract and THC both were rated as possibly effective for improving objective measures of spasticity. Nabiximols likely effectively reduces the severity of spasticity in the short‐term. Centrally mediated pain and painful spasms. Based on the results of four high-quality trials and four low-quality trials, oral cannabis extract was rated as effective, and THC as probably effective in treating central pain and painful spasms. Bladder dysfunction. Based on a single high quality study, oral cannabis extract and THC were rated as probably ineffective for controlling bladder complaints in multiple sclerosis.
Therefore, they require multipurpose plants instead of the dedicated plants prevailing in the industry so far. At the same token, outsourcing is gaining ground. Globalization results in a shift of fine chemical production from the industrialized to developing countries. The latter benefit not only from a "low cost/high skill" advantage, but also from a rapidly rising domestic demand for Western medicine. Despite the mantras of Western industry leaders, the cost advantage of the Asian producers is going to persist. As the pharmerging countries mainly use generics, their market share continues to grow to the detriment of originator pharmaceuticals and agrochemicals. This is also the case for biosimilars, the generic versions of biopharmaceuticals. As a consequence of the harsh business climate, many Western fine chemical companies or divisions created during the "irrational exuberance" at the end of the 20th century have already exited from the sector. Others will follow suit or will be acquired by private equity firms. Survival strategies include implementing lean production principles originally developed by the automotive industry and extending the business model to also include contract research at the beginning and active drug formulation towards the end of the added value chain. This latter strategy, however, is not finding unanimous approval by industry experts.
== Contraindications == Tapentadol is contraindicated in people with epilepsy or who are otherwise prone to seizures. It raises intracranial pressure so should not be used in people with head injuries, brain tumors, or other conditions which increase intracranial pressure. It increases the risk of respiratory depression so should not be used in people with asthma. As with other μ-opioid agonists, tapentadol may cause spasms of the sphincter of Oddi, and is therefore discouraged for use in patients with biliary tract disease such as both acute and chronic pancreatitis. People who are rapid or ultra rapid metabolizers for the CYP2C9, CYP2C19, and CYP2D6 enzymes may not respond adequately to tapentadol therapy. Due to reduced clearance, tapentadol should be administered with caution to people with moderate liver disease and not at all in people with severe liver disease.
Sources: en.wikipedia.org
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and neutral endopeptidases. Semaglutide carries a non-natural amino acid at position eight that blocks that cleavage, and a fatty diacid side chain that binds albumin. The result is a much longer duration of action than the native hormone.
The fatty diacid chain associates strongly with serum albumin, which keeps the peptide in circulation and shields it from rapid renal clearance. Bound peptide is released gradually, producing a sustained receptor signal. This mechanism also reduces the peak-to-trough variation seen with shorter-acting analogues.
The balance between peripheral receptor activation and signalling in the central nervous system is not fully resolved. The extent to which slowed gastric emptying accounts for reduced energy intake, compared with direct effects on appetite circuits, is debated. Long-term effects on lean mass and on tissues outside the gut and brain are still under study.
Purity is commonly expressed as the percentage of the main peak relative to all integrated peaks in a reversed-phase chromatogram. Related substances and counter-ions are reported separately. Values obtained with different detectors are not always directly comparable.