The short version of deamidation fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2025-12-27. 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.
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。
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
| 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 |
Peptides are sensitive to temperature, light, oxygen, and repeated freeze-thaw cycles. Semaglutide in dry form is generally held at refrigerated temperatures, while reconstituted solutions require a defined short-term storage window. Vials should be kept in secondary packaging to limit photodegradation, and exposure to alkaline conditions is avoided because it accelerates chemical degradation. Adsorption to glass and some plastics can reduce the measured concentration of dilute solutions, so low-binding polypropylene containers are preferred for analytical work. Each transfer step introduces a small risk of contamination, and closed handling practices reduce that risk.
Routine characterisation of the peptide relies on reversed-phase high-performance liquid chromatography, often paired with ultraviolet detection near 214 nanometres. Related substances such as deamidated, oxidised, and truncated sequences elute at characteristic positions and are quantified by area percentage. Electrospray ionisation mass spectrometry confirms the molecular mass and can resolve some closely related variants. Peptide mapping after enzymatic digestion provides sequence-level verification and is useful when a full identity profile is required. Method parameters such as column chemistry, gradient, and mobile-phase pH influence the separation and must be reported alongside results.
Serum protein binding dominates the pharmacokinetic profile. The attached chain associates strongly with albumin, shielding the peptide from enzymatic attack and slowing filtration by the kidney. This interaction extends the circulation half-life to roughly one week in humans, which supports weekly administration intervals. An oral version pairs the peptide with an absorption enhancer that transiently alters gastric epithelium, permitting limited uptake; bioavailability by that route is substantially lower than by injection.
Semaglutide belongs to the glucagon-like peptide-1 receptor agonist class, a group of synthetic peptides that imitate an incretin hormone released by intestinal L cells after food intake. Native GLP-1 circulates for only a few minutes because dipeptidyl peptidase-4 cleaves it rapidly. The hormone acts on pancreatic islets, the gastrointestinal tract, and several brain regions. Because the natural peptide is short-lived, development work concentrated on analogues that keep receptor activity while resisting enzymatic breakdown and renal clearance.
As seen in Figure 2, keto acid 1 was generated from the keto aldehyde that was converted to the silyl ether via asymmetric allylboration and silylation of the resulting alcohol. Ozonolysis of the silyl ether and Lindgren–Pinnick oxidation of the aldehyde afforded the keto acid. Ketone 2 was constructed via Enders alkylation starting from the hydrazone. Ozonolysis, the last step of the Enders alkylation, was followed by reduction of the aldehyde and silylation of the resulting alcohol. Hydrogenolysis of the benzyl ether gave the alcohol, which was oxidized under Swern condition and alkylated with the Grignard reagent to yield the secondary alcohol. Oxidation of this alcohol with the Ley–Griffith reagent gave the desired ketone. Thiazole 3 was synthesized from the ester, which was reduced with diisobutylaluminium hydride, and the aldehyde was reacted with the stabilized ylide in the Wittig reaction. Asymmetric allylboration of the α,β-unsaturated aldehyde and protection of the hydroxy group gave the silyl ether, whose terminal olefin was reacted with osmium tetroxide to a diol that was cleaved with lead tetraacetate to furnish the aldehyde. Reduction, iodination, and treatment with triphenylphosphine led to phosphonium salt.
As early as the 1820s, Knoxville's business leaders viewed railroads— then a relatively new form of transportation— as a solution to the city's economic isolation. Led by banker J. G. M. Ramsey (1797–1884), Knoxville business leaders joined calls to build a rail line connecting the city to Cincinnati, Ohio to the north and Charleston, South Carolina to the southeast, which led to the chartering of the Louisville, Cincinnati and Charleston Railroad (LC&C) in 1836. The Hiwassee Railroad, chartered two years later, was to connect this line with a rail line in Dalton, Georgia. In spite of Knoxvillians' enthusiasm (the city celebrated the passage of a state appropriations bill for the LC&C with a 56-gun salute in 1837), the LC&C was doomed by a financial recession in the late 1830s, and construction of the Hiwassee Railroad was stalled by lack of funding amidst continued sectional bickering. The Hiwassee was rechartered as the East Tennessee and Georgia Railroad in 1847, and construction finally began the following year. The first train rolled into Knoxville on June 22, 1855, to great fanfare. With the arrival of the railroad, Knoxville expanded rapidly. The city's northern boundary extended northward to absorb the tracks, and its population grew from about 2,000 in 1850 to over 5,000 in 1860. Local crop prices spiked, the number of wholesaling firms in Knoxville grew from 4 to 14, and two new factories— the Knoxville Manufacturing Company, which made steam engines, and Shepard, Leeds and Hoyt, which built railroad cars— were established.
In the U.S., the Federal Food, Drug, and Cosmetic Act groups skin care products into two main categories: cosmetics and drugs. While prescription drugs must go through a strict approval process before they can be sold, cosmetics do not need FDA approval before being sold, although they are still monitored for labeling, safety, and are regulated. Cosmeceutical and nutricosmetic are marketing terms with no scientific evidence pertaining to skin care or health, and no acceptance for validity as skin care products under US law.
Sources: en.wikipedia.org
=== Contraindications === Labia reduction surgery is relatively contraindicated for the woman who have active gynecological disease, such as an infection or a malignancy; the woman who is a tobacco smoker and is unwilling to quit, either temporarily or permanently, in order to optimize her wound-healing capability; and the woman who is unrealistic in her aesthetic goals. The latter should either be counselled or excluded from labioplastic surgery. Davison et al write that it should not be performed when the patient is menstruating to reduce potential hormonal effects and the increased risk of infection.
Large centralised markets have existed in Hong Kong since at least 16 May 1842, when Central Market was opened. These markets are most frequented by older residents, those with lower incomes, and domestic helpers who serve approximately 10 percent of Hong Kong's residents. Most neighbourhoods contain at least one such market. They have become destinations for tourists to "see the real Hong Kong". Prior to 2000, many of Hong Kong's public markets were managed by the Urban Council (within Hong Kong Island and Kowloon) or the Regional Council (in the New Territories). Since 2000, Hong Kong's public markets have been regulated by the Food and Environmental Hygiene Department. Under the Slaughterhouse Regulation, the slaughtering of live bovine animals, swine, goats, sheep or soliped for human consumption must take place in a licensed slaughterhouse, None of the markets in Hong Kong hold wild or exotic animals. In 2018, the FEHD operated 74 markets housing approximately 13,070 stalls. In addition, the Hong Kong Housing Authority operated 21 markets while private developers operated about 99 (in 2017).
==== Respiratory syncytial virus (Human orthopneumovirus) ==== Sendai virus was also used as a backbone for vaccine against respiratory syncytial virus (HRSV). This virus (HRSV), is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. It was shown that administration of SeV-based RSV vaccine protects cotton rats and African green monkeys from this viral infection. The HRSV phase I clinical trial was completed in adults. It demonstrated high safety of the SeV-based construct that expressed HRSV envelope F glycoprotein.
Sources: en.wikipedia.org
The idea is to provoke, surprise and delight the diner." elBulli was only open for about six months of the year, from mid-June to mid-December. Adrià spent the remaining six months of the year perfecting recipes in the workshop "elBulliTaller" in Barcelona. The restaurant closed on 30 July 2011. It reopened as a creativity center to foster innovation like his own and entirely new ideas in 2014. elBulli had 3 Michelin stars and was one of the best restaurants in the world. It received first place in the Restaurant Top 50 in 2002. Then in 2005, it ranked second. It was again awarded the first place in 2006, and retained this title in 2007, 2008 and 2009, making a record 5 times in the top spot. In 2010, after elBulli announced it would close for good the next season, the title was awarded to Noma of Copenhagen, Denmark. Adrià is well known for creating "culinary foam". Adrià explored foams created without the addition of cream or egg white; foams are made of a flavoured liquid and an additive (such as lecithin), then aerated through a variety of methods, including whipping with an immersion blender or extrusion from a siphon bottle equipped with N2O cartridges. Further culinary processes (such as freeze-drying or freezing with liquid nitrogen) may be applied to foams as well. Using a single flavoured liquid allows the flavour of the final product to be less diluted and thus more intense. Adrià is the author of several cookbooks including A Day at El Bulli, El Bulli 2003–2004 and Cocinar en Casa (Cooking at Home).
2003 First evidence that aging of nematodes is regulated via TOR signaling. 2003 The Methuselah Foundation is organized by Aubrey de Grey and David Gobel to create life extension technologies based on the Strategies for engineered negligible senescence (SENS) approaches and supporting related research in other organizations. 2003 Andrzej Bartke created a mouse that lived 1,819 days (8 days short of 5 years), while the maximum lifespan for this species is 1,030–1,070 days. By human standards, such longevity is equivalent to about 180 years. 2004 First evidence that aging of nematodes is regulated by AMP-Kinase. 2004 Aubrey de Grey coined the term "longevity escape velocity" (LEV). Though the concept per se has been present in the life extension community since at least the 1970s (for example, Robert Wilson, essay Next Stop, Immortality, 1978). 2004 As a result of the use of anti-aging therapy, a team of scientists led by Stephen Spindler managed to extend the life of a group of already adult mice to an average of 3.5 years. For this achievement, the first Methuselah Mouse Rejuvenation 'M Prize' was awarded. 2004 Creation of the first curated database of genes related to human ageing: GenAge. 2006 Creation of induced stem cells (iSC) from somatic cells by the simultaneous action of several factors. First produced by the Japanese scientist Shinya Yamanaka. In 2012, Shinya Yamanaka and John Gurdon received the Nobel Prize for their work on reprogramming mature cells into pluripotent cells. 2007 Extension of mouse lifespan via deletion of insulin receptor in the brain.
== Function == Vitamin D-binding protein belongs to the albumin gene family, together with human serum albumin and alpha-fetoprotein. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid (CSF), and on the surface of many cell types. It binds to various forms of vitamin D, including ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), the 25-hydroxylated forms (calcifediol), and the active hormonal product, 1,25-dihydroxyvitamin D (calcitriol). The major proportion of vitamin D in blood is bound to this protein. Once bound, it transports vitamin D and its plasma metabolites between the skin, liver, and kidney, and then on to the various target tissues. The expression of GC, and therefore the production of GC Vitamin D binding protein, is restricted towards the liver; in an RNA-sequence (RNA-seq) study of tissues samples from 95 human individuals across 27 tissue representations analysed on December 19, 2024, GC was expressed primarily in the tissue of the liver, at a mean RPKM (reads per kilobase million) value of 1258.79 ± 214.721 across 3 samples. In comparison, the next highest RPKM means were in the anatomically nearby gallbladder, at a value of 235.12 ± 73.639 across 3 samples, followed by the stomach, at a value of 23.974 ± 19.053 across 3 samples, the duodenum, at a value of 22.508 ± 6.514 across 2 samples, and the kidney, at a value of 12.033 ± 12.168 across 4 samples. Other tissue samples held a negligible value in comparison to the liver, gallbladder, stomach, duodenum, and kidney.
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.
差别集中在三处：第 8 位残基被非天然氨基酸取代，第 34 位换成精氨酸，第 26 位增加一条脂肪酸侧链。前两处改动降低酶解速率，侧链则通过白蛋白结合延长循环时间。综合结果是半衰期从约两分钟延长到约一周。