The short version of 脂肪酸酰化 fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-03-05. Anything still debated is marked as such rather than presented as settled.
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.
Semaglutide dissolves readily in water and in aqueous buffers near neutral pH. Solubility decreases near the isoelectric point, where net charge is minimal. Common laboratory solvents include phosphate-buffered saline and dilute ammonium bicarbonate. Strongly acidic or basic conditions may accelerate hydrolysis. Working concentrations are usually prepared by diluting a concentrated stock. Vial surfaces can adsorb small amounts of peptide at low concentrations, so carrier proteins or low-binding tubes are sometimes used.
Reverse-phase high-performance liquid chromatography is the standard method for purity assessment, separating the peptide from truncated or oxidized variants. Mass spectrometry confirms molecular mass and detects modifications, while ultraviolet absorbance near 280 nanometers supports concentration measurement through tryptophan and tyrosine residues. Circular dichroism can indicate secondary structure, though the peptide is largely helical in solution, and ion-exchange chromatography resolves charge variants. Purity values above 95 percent are typical for research-grade material. Stability studies track degradation over time under defined conditions.
| 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 |
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.
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.
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
Semaglutide 是一种经结构修饰的胰高血糖素样肽-1 类似物，其主链与内源性 GLP-1(7-36) 约有百分之九十四的序列一致性。第 8 位丙氨酸被 α-氨基异丁酸取代，使二肽基肽酶-4 无法识别原有切割位点。第 34 位赖氨酸换为精氨酸，进一步降低酶解速率。第 26 位赖氨酸经间隔基连接一条含十八个碳的二酸脂肪链，该侧链赋予分子与血浆白蛋白结合的能力。
Typically, the higher the temperature the kiln operates at, the larger amount of emissions are produced (per pound of water removed). This is especially true in the drying of thin veneers and high-temperature drying of softwoods.
Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions using an electrospray in which a high voltage is applied to a liquid to create an aerosol. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized. ESI is different from other ionization processes (e.g. matrix-assisted laser desorption/ionization, MALDI) since it may produce multiple-charged ions, effectively extending the mass range of the analyser to accommodate the kDa-MDa range observed in proteins and their associated polypeptide fragments. Mass spectrometry using ESI is called electrospray ionization mass spectrometry (ESI-MS) or, less commonly, electrospray mass spectrometry (ES-MS). ESI is a so-called 'soft ionization' technique, since there is very little fragmentation. This can be advantageous in the sense that the molecular ion (or more accurately a pseudo molecular ion) is almost always observed, however very little structural information can be gained from the simple mass spectrum obtained. This disadvantage can be overcome by coupling ESI with tandem mass spectrometry (ESI-MS/MS). Another important advantage of ESI is that solution-phase information can be retained into the gas-phase. The electrospray ionization technique was first reported by Masamichi Yamashita and John Fenn in 1984, and independently by Lidia Gall and co-workers in Soviet Union, also in 1984. Gall's work was not recognised or translated in the western scientific literature until a translation was published in 2008.
== External links == Motilin at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Nosek TM. "Section 6/6ch2/s6ch2_26". Essentials of Human Physiology. Archived from the original on 2016-03-24.
ΔG0 – empirically derived offset that in part corresponds to the overall loss of translational and rotational entropy of the ligand upon binding. ΔGhb – contribution from hydrogen bonding ΔGionic – contribution from ionic interactions ΔGlip – contribution from lipophilic interactions where |Alipo| is surface area of lipophilic contact between the ligand and receptor ΔGrot – entropy penalty due to freezing a rotatable in the ligand bond upon binding A more general thermodynamic "master" equation is as follows:
Sources: en.wikipedia.org
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life. Amino acids can be classified according to the locations of the core structural functional groups (alpha- (α-), beta- (β-), gamma- (γ-) amino acids, etc.); other categories relate to polarity, ionization, and side-chain group type (aliphatic, acyclic, aromatic, polar, etc.). In the form of proteins, amino-acid residues form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life on Earth and its emergence. Amino acids are formally named by the IUPAC-IUBMB Joint Commission on Biochemical Nomenclature in terms of the fictitious "neutral" structure shown in the illustration. For example, the systematic name of alanine is 2-aminopropanoic acid, based on the formula CH3−CH(NH2)−COOH. The Commission justified this approach as follows:
Tendinopathy (tendinitis, U.S. English) is a type of tendon disorder that results in pain, swelling, and impaired function. It most commonly occurs around larger joints, including the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbow, golfer's elbow), wrist, hip, knee (jumper's knee), or ankle (Achilles tendinitis). Causes may include trauma or repetitive activities. Less common causes include infection, arthritis, gout, thyroid disease, diabetes and the use of quinolone antibiotic medicines. Groups at risk include manual laborers, musicians, and sports participants. Diagnosis is typically based on symptoms, examination, and imaging. Typically, little inflammation remains after a few weeks, assuming that the underlying problem is related to weak or disrupted tendon fibrils. Treatment options include rest, NSAIDs, splinting, and physiotherapy. Steroid injections, surgery, or shockwave therapy may be appropriate. About 80% of overuse tendinopathy patients recover completely within six months. Tendinopathy is relatively common. Older people are most commonly affected.
In 1924, indium was found to have a valued property of stabilizing non-ferrous metals, and that became the first significant use for the element. The first large-scale application for indium was coating bearings in high-performance aircraft engines during World War II, to protect against damage and corrosion; this is no longer a major use of the element. New uses were found in fusible alloys, solders, and electronics. In the 1950s, tiny beads of indium were used for the emitters and collectors of PNP alloy-junction transistors. In the middle and late 1980s, the development of indium phosphide semiconductors and indium tin oxide thin films for liquid-crystal displays (LCD) aroused much interest. By 1992, the thin-film application had become the largest end use. Indium(III) oxide and indium tin oxide (ITO) are used as a transparent conductive coating on glass substrates in electroluminescent panels. Indium tin oxide is used as an infrared radiation filter in low-pressure sodium-vapor lamps. The infrared radiation is reflected back into the lamp, which increases the temperature within the tube and improves the performance of the lamp. Indium has many semiconductor-related applications. Some indium compounds, such as indium antimonide and indium phosphide, are semiconductors with useful properties: one precursor is usually trimethylindium (TMI), which is also used as the semiconductor dopant in II–VI compound semiconductors. InAs and InSb are used for low-temperature transistors and InP for high-temperature transistors.
Sources: en.wikipedia.org
==== Wound healing ==== Nanogels are a promising technology being explored to aid in the wound healing process. Given their ability to encapsulate various types of cargo, nanogels can strategically deliver anti-inflammatory agents, antimicrobial drugs, and necessary growth factors to facilitate new tissue growth and blood vessel formation. Chitosan-based nanogels have demonstrated an improved wound healing effect in previous studies. Chitosan-based nanogels encapsulating interleukin-2 were successfully used to stimulate the immune system and advance the wound healing process. Additionally, chitosan-based nanogels carrying an antibiotic, silver sulfadiazine, were found to decrease the size of second-degree burns in one in vivo study. In another study, silver-loaded nanogels were synthesized in a natural polymer-based solution containing aloe vera, and the presence of aloe vera led to increased healing and a decrease in wound size. With the goal of preventing infection and accelerating the healing process, one group has also published a new nanogel design consisting of an encapsulating core and a functionalized outer surface capable of targeting bacteria present in wounds.
The tea served on New Year's Day and at weddings is sometime kelp tea because the pronunciation of kombu is similar to that of the last part of "yorokobu" (喜ぶ, meaning "be happy"). Fuku-cha(福茶, meaning "fortune tea") is sencha green tea with kombu, umeboshi (pickled plum), kuromame (black beans), and sanshō (Japanese pepper) and is drunk on the last day of the year (Ōmisoka), in New Year, and on the day before the beginning of spring (Setsubun) in Kansai region, wishing a long life. In particular, in New Year, oo-buku-cha or dai-buku-cha (大福茶, meaning "very good fortune tea"), which is sencha green tea with kombu and umeboshi, is drunk in Kansai region wishing good health and happiness.
The UK government says that a report published on the GOV.UK website on 27 December that said housing asylum seekers on the Bibby Stockholm barge was discriminatory on the grounds of age and sex was published by mistake. The report is deleted from the website. 30 December Eurostar services to and from London St Pancras are cancelled because of a flood in a tunnel under the River Thames. British Army officer Preet Chandi becomes the fastest woman to complete a trek to the South Pole on skis. Four police officers are injured and eight people arrested following a demonstration in Camberwell, south London, relating to tensions in the local Eritrean community. 31 December American XL bully dogs are added to the list of banned species under the Dangerous Dogs Act 1991 in England and Wales, requiring them to be on a lead and muzzled in public. It is also illegal to breed, sell or abandon the dogs. Eurostar resumes services to and from London St Pancras following the previous day's disruption. Two people killed in an avalanche at the French ski resort of Saint-Gervais-les-Bains on 28 December are named as British mother and son Kate and Archie Vokes.
1904: American geographer, geologist and educator Zonia Baber published her article "The Scope of Geography", in which she laid out her educational theories on the teaching of geography. She argued that students required a more interdisciplinary, experiential approach to learning geography: instead of a reliance on textbooks, students needed field-trips, lab work and map-making knowledge. Baber's educational ideas transformed the way schools taught geography. 1904: British chemists Ida Smedley, Ida Freund and Martha Whiteley organized a petition asking the Chemical Society to admit women as Fellows. A total of 19 female chemists became signatories, but their petition was denied by the society. 1904: Marie Stopes was a British author, palaeobotanist and campaigner for women's rights. She made significant contributions to plant palaeontology and coal classification. She held the post of Lecturer in Palaeobotany at the University of Manchester from 1904 to 1910; in this capacity she became the first female academic of that university. In 1909, she was elected to the Linnean Society of London. She was 26 at the time of her election to Fellowship (the youngest woman admitted at that time). 1904: In a December meeting, the Linnean Society of London elected its first women Fellows. These initial women included horticulturalist Ellen Willmott, ornithologist Emma Turner, biologist Lilian Jane Gould, mycologists Gulielma Lister and Annie Lorrain Smith, and botanists Mary Anne Stebbing, Margaret Jane Benson and Ethel Sargant.
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.
Long-term storage is usually at minus 20 to minus 80 degrees Celsius in a sealed, desiccated container. Working aliquots can be held briefly at 2 to 8 degrees Celsius.