aggregation raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
This page was last updated on 2025-11-16 and is reviewed periodically as new material appears.
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.
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.
市售注射用制剂通常要求在二至八摄氏度冷藏保存，并避免光照与冻结。部分多剂量笔在首次使用后允许在不超过三十摄氏度的环境中存放有限周数，具体期限由辅料与防腐剂体系决定。反复冻融会促进肽链聚集并改变可见颗粒计数，因此应予避免。冻干粉末在干燥、避光、低温条件下更为稳定。溶液配制后宜使用低吸附容器，以减少肽类在塑料或玻璃表面的损失。
纯度评价多采用反相高效液相色谱，流动相常加入三氟乙酸或甲酸作为离子对改性剂，检测波长设在二百一十四纳米或二百二十纳米。分子量确认依靠电喷雾电离质谱或基质辅助激光解吸电离质谱，实测值应与理论值在数 ppm 内吻合。肽图分析通过酶切后液相色谱串联质谱完成，用于核查序列与修饰位点。体积排阻色谱用于定量共价与非共价聚集体。生物基质浓度测定则采用免疫分析或液相色谱串联质谱。
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | free base, without counter-ion |
| Molecular weight | About 4114 Da | peptide backbone plus attached lipid chain |
| Plasma half-life | About 165 hours | supports once-weekly dosing in humans |
| Plasma protein binding | Greater than 99 percent | attributed mainly to serum albumin |
| Receptor target | GLP-1 receptor | Gs-coupled, raises intracellular cyclic AMP |
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 or 280 nanometres is widely used to assess purity and to resolve related impurities. Liquid chromatography coupled to mass spectrometry confirms identity through the protonated molecular ion and fragment ions formed in tandem experiments. Capillary electrophoresis and peptide mapping after enzymatic digestion supply complementary information on charge variants and modification sites. Circular dichroism and nuclear magnetic resonance can report on secondary structure in solution. Absolute quantification usually depends on an external standard, and reported purity depends on the detection wavelength and integration parameters chosen.
Lyophilised material appears as a white to off-white cake or powder that is hygroscopic, and containers are usually equilibrated to room temperature before opening to limit condensation. Dissolution is performed in water, phosphate-buffered saline, or a mildly alkaline buffer, since solubility rises above neutral pH. Gentle inversion or low-speed mixing is preferred, because vigorous vortexing can promote surface denaturation and aggregation. Complete dissolution may require several minutes, and brief sonication is sometimes applied. Passing the solution through a 0.22 micrometre membrane removes particulates but does not by itself sterilise the liquid.
Storage at minus 20 degrees Celsius or lower in a desiccated container preserves the peptide for extended periods, while working solutions are commonly held at two to eight degrees Celsius for short intervals. Light exposure and repeated freeze-thaw cycles accelerate degradation, so dividing material into single-use aliquots is generally recommended. Adsorption to glass and plastic surfaces can lower the measured concentration of dilute solutions, particularly below one milligram per millilitre. The degradation routes most often reported for GLP-1 analogues are deamidation, methionine oxidation, and backbone hydrolysis. Relative rates under specific conditions are frequently described only for individual formulations.
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.
Plaques on house exteriors inform pedestrians where a well-known personality once lived. Often, these plaques are dedicated to Soviet celebrities little known outside Russia (and similarly, for decorated generals and revolutionaries, little known inside Russia). In addition, Moscow contains many "museum houses" dedicated to famous Russian writers, composers, and artists. Moscow's skyline is rapidly modernizing, with several new towers being constructed. In recent years, the city administration has been widely criticized for the widespread destruction of many historical buildings. As much as a third of historic Moscow has been destroyed during the past few years to make space for luxury apartments and hotels. Other historical buildings—including landmarks such as the 1930 Moskva hotel and the 1913 department store Voyentorg—have been razed and rebuilt, with an inevitable loss in historical value. Critics blame the government for not enforcing conservation laws: during the last 12 years, more than 50 buildings with monument status were torn down, several of these dating back to the 17th century. In addition, some critics wonder if the funds used for reconstructing razed buildings could not be used to renovate decaying structures—such as many works of architect Konstantin Melnikov, as well as the Mayakovskaya metro station. Some organizations, such as the Moscow Architecture Preservation Society and Save Europe's Heritage, are trying to attract international public attention to these problems.
Primary antioxidants scavenge free radicals formed during the initial (thermal) oxidation process (ROO•), thus preventing chain reactions that lead to polymer degradation. Examples: butylated hydroxytoluene, 2,4-dimethyl-6-tert-butylphenol, para tertiary butyl phenol, 2,6-di-tert-butylphenol, 1,3,5-Tris(4-(tert-butyl)-3-hydroxy-2,6-dimethylbenzyl)-1,3,5-triazinane-2,4,6-trione
Prolyl endopeptidase is a large cytosolic enzyme that belongs to a distinct class of serine peptidases. It was first described in the cytosol of rabbit brain as an oligopeptidase, which degrades the nonapeptide bradykinin at the Pro-Phe bond. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides such as alpha-melanocyte-stimulating hormone, luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone, angiotensin, neurotensin, oxytocin, substance P and vasopressin. PREP cleaves peptide bonds at the C-terminal side of proline residues. Its activity is confined to action on oligopeptides of less than 10 kD and it has an absolute requirement for the trans-configuration of the peptide bond preceding proline. Prolyl endopeptidases are involved in the maturation and degradation of peptide hormones and neuropeptides.
Lockheed implemented it into the L-1011 TriStar in 1973 at the request of Pacific Southwest Airlines (who used the baggage compartment as an entertainment lounge) and possibly also to suit potential Soviet buyers (see below). In October 1967, the Soviet government approved a Ministry of Civil Aviation (Aeroflot) specification for an aerobus. This called for 350 seats and a range of 3,600 kilometres (1,900 nautical miles) with a 40-tonne payload or 5,800 km (3,100 nmi) with seats taken but no freight. The airliner had to operate from smaller airports (classified as Klass "B" and "V" [Russian: класс "Б", "В"] or "Class B/C" by the Soviets) 2,600-metre (8,500 ft) runways. In the second half of the 1960s, OKB-240 (as the Ilyushin bureau was formally known) was restoring positions lost (with Yakovlev, in favour of Tupolev and Antonov) during the Khrushchev era and was well placed to secure design of the aerobus. When the Soviet cabinet's defence industry committee promoted the Aeroflot specification on September 8, 1969, to a preliminary project, (Russian: аванпроект; transliterated: avanproyekt), it entrusted it to Ilyushin. The bureau received specific operational requirements for the aerobus on February 22, 1970. In developing the concept which had been agreed, Ilyushin faced four challenges: configuration (layout or "shape"), powerplant, automation (avionics) and manufacturing capacity.
== Biological roles == Human uses of AGPs include the use of gum arabic in the food and pharmaceutical industries because of natural properties in thickening and emulsification. AGPs in cereal grains have potential applications in biofortification, as sources of dietary fibre to support gut bacteria and protective agents against ethanol toxicity. AGPs are found in a wide range of plant tissues, in secretions of cell culture medium of root, leaf, endosperm and embryo tissues, and some exudate producing cell types such as stylar canal cells. AGPs have been shown to regulate many aspects of plant growth and development including male-female recognition in reproduction organs, cell division and differentiation in embryo and post-embryo development, seed mucilage cell wall development, root salt tolerance and root-microbe interactions. These studies suggest that they are multifunctional, similar to what is found in mammalian proteoglycans/glycoproteins. Conventional methods to study functions of AGPs include the use of β-glycosyl (usually glucosyl) Yariv reagents and monoclonal antibodies (mAbs). β-Glycosyl Yariv reagents are synthetic phenylazo glycoside probes that specifically, but not covalently, bind to AGPs and can be used to precipitate AGPs from solution. They are also used commonly as histochemical stains to probe the locations and distribution of AGPs. A number of studies have shown that addition of β-Yariv reagents to plant growth medium can inhibit seedling growth, cell elongation, block somatic embryogenesis and fresh cell wall mass accumulation.
Sources: en.wikipedia.org
== Isobaric carrier concept == TMT tags are commonly used to label samples of equal abundance. If one of the labeled samples is more abundant, however, it may increase the sensitivity of the analysis for all samples. Such isobarically labeled samples are referred to as isobaric carriers. They were introduced for single-cell protein analysis by mass spectrometry, and have found many other applications.
The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.
Genetically modified crops ("GM crops", or "biotech crops") are plants used in agriculture, the DNA of which has been modified with genetic engineering techniques. In most cases, the main aim is to introduce a new trait that does not occur naturally in the species. Biotechnology firms can contribute to future food security by improving the nutrition and viability of urban agriculture. Furthermore, the protection of intellectual property rights encourages private sector investment in agrobiotechnology. Examples in food crops include resistance to certain pests, diseases, stressful environmental conditions, resistance to chemical treatments (e.g. resistance to a herbicide), reduction of spoilage, or improving the nutrient profile of the crop. Examples in non-food crops include production of pharmaceutical agents, biofuels, and other industrially useful goods, as well as for bioremediation. Farmers have widely adopted GM technology. Between 1996 and 2011, the total surface area of land cultivated with GM crops had increased by a factor of 94, from 17,000 to 1,600,000 square kilometers (4,200,000 to 395,400,000 acres). 10% of the world's crop lands were planted with GM crops in 2010. As of 2011, 11 different transgenic crops were grown commercially on 395 million acres (160 million hectares) in 29 countries such as the US, Brazil, Argentina, India, Canada, China, Paraguay, Pakistan, South Africa, Uruguay, Bolivia, Australia, Philippines, Myanmar, Burkina Faso, Mexico, and Spain.
Harvests are by necessity a speedy affair: after blossoming at dawn, flowers quickly wilt as the day passes. All plants bloom within a window of one or two weeks. Stigmas are dried quickly upon extraction and (preferably) sealed in airtight containers.
== Regulations and management == These are tactics and methods that aim to remediate the effects of certain, or all, CEC by preventing movement throughout the environment, or limiting their concentrations in certain environmental systems. It is particularly important to ensure that water treatment approaches do not simply move contaminants from effluent to sludge given the potential for sludge to be spread to land providing an alternative route to entering the environment.
Sources: en.wikipedia.org
In the United States alone, sales of the Invega franchise (including Sustenna, Trinza, and Hafyera) reached $3.1 billion in 2024, an 8% increase over the previous year. The market is served primarily by Janssen Pharmaceuticals, with generic competition expected to begin after the key U.S. patent expires on January 26, 2031.
==== Illegal marketing settlement (2014) ==== In June 2010, health insurance network Blue Cross Blue Shield (BCBS) filed a lawsuit against Pfizer for allegedly illegally marketing drugs Bextra, Geodon and Lyrica. BCBS alleged that Pfizer used kickbacks and wrongly persuaded doctors to prescribe the drugs. According to the lawsuit, Pfizer handed out 'misleading' materials on off-label uses, sent over 5,000 doctors on trips to the Caribbean or around the United States, and paid them $2,000 honoraria in return for listening to lectures about Bextra. Despite Pfizer's claims that "the company's intent was pure" in fostering a legal exchange of information among doctors, an internal marketing plan revealed that Pfizer intended to train physicians "to serve as public relations spokespeople." The case was settled in 2014 for $325 million. Fearing that Pfizer is "too big to fail" and that prosecuting the company would result in disruptions to Medicare and Medicaid, federal prosecutors instead charged a subsidiary of a subsidiary of a subsidiary of Pfizer, which is "nothing more than a shell company whose only function is to plead guilty."
Other techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by a prion. The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is likely to be benign.
=== Israeli−Palestinian conflict === Hitchens described Zionism as "an ethno-nationalist quasi-religious ideology" but argued that Zionism "nonetheless has founded a sort of democratic state which isn't any worse in its practice than many others with equally dubious origins." He stated that Israeli settlements on Palestinian territory to achieve security for Israel are "doomed to fail in the worst possible way", and the cessation of this "appallingly racist and messianic delusion" would "confront the internal clerical and chauvinist forces which want to instate a theocracy for Jews". Hitchens contended that the "solution of withdrawal would not satisfy the jihadists" and wondered "What did they imagine would be the response of the followers of the Prophet [Muhammad]?" Hitchens bemoaned the transference of Arab secularism into religious terrorism as a means of democratisation: "the most depressing and wretched spectacle of the past decade, for all those who care about democracy and secularism, has been the degeneration of Palestinian Arab nationalism into the theocratic and thanatocratic hell of Hamas and Islamic Jihad". On 14 November 2004, Hitchens noted:
Surgical technique – the septal mucosal flap The surgeon cuts the anteriorly based septal mucosal tissue-flap as widely as possible, and then releases it with a low, posterior back-cut; but only as required to allow the rotation of the tissue-flap into the nasal wound.
Sources: en.wikipedia.org
Native GLP-1 is a short-lived peptide cleared within one to two minutes by dipeptidyl peptidase-4 and related enzymes. Semaglutide keeps the receptor-binding backbone but adds substitutions and a lipid chain. These changes block the main cleavage site and allow reversible albumin binding, extending the half-life to roughly 165 hours.
Albumin is the most abundant protein in plasma and carries molecules that bear fatty-acid chains. Binding shields the peptide from renal filtration and from peptidases, keeping a circulating reservoir. Slow release from this reservoir produces sustained receptor occupancy and supports infrequent dosing.
The insulinotropic effect is glucose-dependent, meaning secretion increases mainly when glucose is elevated. This property is often described as lowering the chance of hypoglycaemia when the compound is used alone. Other glucose-lowering agents used at the same time can still cause low blood glucose.
冻融过程中冰晶形成与局部浓度升高会促使肽链发生界面吸附和聚集。聚集不仅降低有效含量，还会改变可见异物与不溶性微粒的计数结果。将溶液分装为单次使用的小体积等份可减少循环次数。