A practical reference on deamidation: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2025-09-04 and is reviewed periodically as new material appears.
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。
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.
| Property | Value | Notes |
|---|---|---|
| 分子式 | C187H291N45O59 | 按主链与 C18 二酸侧链计算 |
| 分子量 | 约 4113.6 道尔顿 | 游离碱形式，随反离子略有差异 |
| 外观 | 白色至类白色冻干粉末 | 具吸湿性，需干燥保存 |
| 溶解性 | 微溶于水，易溶于碱性缓冲液 | 溶解性随 pH 升高而改善 |
| 等电点 | 约 5.4 | 影响缓冲液选择与聚集倾向 |
Stability studies examine how temperature, pH, and moisture influence degradation rates over time. In aqueous solution, hydrolysis and deamidation accelerate as pH moves away from mildly acidic conditions. Light exposure and residual metal ions can also trigger oxidation of susceptible residues. Accelerated aging at elevated temperature is used to estimate shelf life, though extrapolation to room temperature carries uncertainty because individual degradation pathways do not always scale predictably.
Lyophilized semaglutide powder is typically held at minus twenty degrees Celsius for long-term storage. At that temperature, solid-state degradation reactions proceed slowly and the peptide remains intact for extended periods. Repeated freeze-thaw cycles are best avoided because they promote aggregation and can shift the proportion of monomeric peptide present. Working aliquots are often prepared so that each portion is thawed only once, and desiccant is placed inside the vial to limit moisture uptake.
Identity and purity are usually assessed by reverse-phase high-performance liquid chromatography coupled to mass spectrometry. Retention time and observed mass are compared against a reference standard run under identical conditions. Impurity profiles reveal deamidation products, oxidized methionine variants, and truncated fragments that arise during synthesis or storage. Peptide mapping through enzymatic digestion confirms the primary sequence, while amino acid analysis offers an independent check on overall composition.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 nm is the standard purity method, reported as area percent. Mass spectrometry, usually with electrospray ionisation, confirms identity and reveals covalent modifications. Size-exclusion chromatography quantifies aggregates and fragments. Peptide mapping after enzymatic digestion localises changes to specific sequence regions. Circular dichroism and infrared spectroscopy report on secondary structure, while light scattering tracks particle formation in liquid formulations. No single technique captures every quality attribute.
Quality control relies on pharmacopoeial monographs where they exist, combined with in-house specifications for identity, purity, water content, and counter-ion composition. Reference standards allow calibration across laboratories, although certified materials for every analogue are not universally obtainable. Batch records, chromatograms, and mass spectra form the documentation trail. Regulatory classification varies by jurisdiction and intended use, and research-grade material differs from pharmaceutical-grade material in testing scope. Analytical uncertainty is often expressed as relative standard deviation across replicate injections.
Lyophilised semaglutide is generally held at -20 °C or below, protected from light and moisture. Reconstituted solutions are typically kept at 2-8 °C and used within a defined window because degradation accumulates over time. Repeated freeze-thaw cycles are discouraged, since each cycle can promote aggregation and reduce monomeric content. Room-temperature stability of the solid has been examined in some studies but remains incompletely characterised for long durations, so cold storage is the conservative default for research material.
The distinction between established facts and open questions matters here. That the peptide binds the GLP-1 receptor and stimulates insulin release in a glucose-dependent manner is well documented. How individual variability in receptor density, gastric emptying rate, and gut microbiome composition shapes response remains an active research area. Long-term outcomes beyond five years of continuous use are not yet fully characterized in published trials, and several extension studies are ongoing.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L cells after food intake. The molecule is a 31-amino-acid backbone modified at three positions to resist cleavage by dipeptidyl peptidase-4, the enzyme that degrades native GLP-1 within minutes. A lysine residue at position 26 carries a linker and a C18 fatty diacid, which promotes binding to serum albumin and slows renal clearance. These changes extend the circulating half-life from roughly two minutes to about one week in humans.
Duterte also used the US-Philippines Visiting Forces Agreement as leverage in securing vaccines from the United States, threatening to scrap the military pact. In addition, in an apparent effort to help the Philippines gain access to US-developed vaccines, Duterte granted absolute pardon to US soldier Joseph Scott Pemberton, who was serving prison for killing transgender Jennifer Laude in 2014.
The Qatar corruption scandal at the European Parliament, also known as Qatargate, is a cash-for-influence investigation into several Members of the European Parliament and their associates, who are accused of accepting cash and gifts from Qatar and Morocco in return for promoting the interests of those countries in the European Union. The scandal broke on 9 December 2022, when police raided properties in Brussels, seized over €1 million in cash, and arrested a number of suspects, including Greek MEP and Vice-President of the European Parliament Eva Kaili and her partner Francisco Giorgi, a parliamentary assistant. Also detained were Antonio Panzeri, head of an NGO and a former Italian MEP, and Niccolò Figà-Talamanca, head of an NGO. Kaili denied charges of corruption, money-laundering and belonging to a criminal organisation, while her partner admitted his role in the affair. Panzeri agreed to a plea-deal, providing information to the police in return for a reduced sentence. Figà-Talamanca denied the charges. In February 2023, MEPs Marc Tarabella and Andrea Cozzolino were arrested and charged; both deny wrong-doing. In early 2025, former Belgian MEP Marie Arena was charged with belonging to a criminal organisation, which she denies. The origins of the investigation into the scandal date from the spring of 2022, when Belgian security services mounted a surveillance operation against Panzeri, following a tip-off from another European intelligence service that he had been accepting bribes from Morocco.
KFC's core product offering is pressure fried on-the-bone chicken pieces seasoned with Colonel Harland Sanders' "Original Recipe" of 11 herbs and spices. The product is typically available in either two- or three-piece individual servings or in a family size cardboard bucket typically holding between six and 16 chicken pieces. In territories that follow the system handed down by Colonel Sanders, such as Canada and the UK, each chicken is divided into nine different cuts (two drumsticks, two thighs, two wings, two breast pieces and one keel); however, the United States now uses an eight-piece cut. The chicken is hand-breaded at individual KFC outlets with wheat flour mixed with seasoning in a two- to four-minute process. It is then pressure fried for between seven and 10 minutes (the timing differs between countries) in oil at 185 degrees Celsius. Following this, the chicken is left to stand for 5 minutes in order for it to sufficiently cool before it is placed in the warming oven. It is KFC policy to discard chicken if it has not been sold within 90 minutes in order to ensure freshness. The frying oil varies regionally and versions used include sunflower, soybean, rapeseed and palm oil. A KFC executive stated that the taste of the chicken will vary between regions depending on the oil variety used and whether the chicken has been corn-fed or wheat-fed.
== Further reading == Reilly, Bernard F. (1988). "The Reconstitution of León-Castilla". The Kingdom of León-Castilla under King Alfonso VI, 1065–1109. Princeton: Princeton University Press. pp. 3–13. ... the hilltop, fortress city of Coimbra fell, after a six-month siege, on July 25, 1064.
Because radon is quite electropositive for a noble gas, it is possible that radon fluorides actually take on highly fluorine-bridged structures and are not volatile. Extrapolation down the noble gas group would suggest also the possible existence of RnO, RnO2, and RnOF4, as well as the first chemically stable noble gas chlorides RnCl2 and RnCl4, but none of these have yet been found. Radon carbonyl (RnCO) has been predicted to be stable and to have a linear molecular geometry. The molecules Rn2 and RnXe were found to be significantly stabilized by spin-orbit coupling. Radon caged inside a fullerene has been proposed as a drug for tumors. Despite the existence of Xe(VIII), no Rn(VIII) compounds have been claimed to exist; RnF8 should be highly unstable chemically (XeF8 is thermodynamically unstable). Radon reacts with the liquid halogen fluorides ClF, ClF3, ClF5, BrF3, BrF5, and IF7 to form RnF2. In halogen fluoride solution, radon is nonvolatile and exists as the RnF+ and Rn2+ cations; addition of fluoride anions results in the formation of the complexes RnF3− and RnF42−, paralleling the chemistry of beryllium(II) and aluminium(III). The standard electrode potential of the Rn2+/Rn couple has been estimated as +2.0 V, although there is no evidence for the formation of stable radon ions or compounds in aqueous solution.
Sources: en.wikipedia.org
The pore sizes of technical membranes are specified differently depending on the manufacturer. One common distinction is by nominal pore size. It describes the maximum pore size distribution and gives only vague information about the retention capacity of a membrane. The exclusion limit or "cut-off" of the membrane is usually specified in the form of NMWC (nominal molecular weight cut-off, or MWCO, molecular weight cut off, with units in Dalton). It is defined as the minimum molecular weight of a globular molecule that is retained to 90% by the membrane. The cut-off, depending on the method, can by converted to so-called D90, which is then expressed in a metric unit. In practice the MWCO of the membrane should be at least 20% lower than the molecular weight of the molecule that is to be separated. Using track etched mica membranes Beck and Schultz demonstrated that hindered diffusion of molecules in pores can be described by the Rankin equation. Filter membranes are divided into four classes according to pore size:
== External links == Synopsis of Chapter 5, Campbell & Reece, 2002 Lecture notes on the structure and function of macromolecules Archived 2009-03-26 at the Wayback Machine Several (free) introductory macromolecule related internet-based courses Archived 2011-07-18 at the Wayback Machine Giant Molecules! by Ulysses Magee, ISSA Review Winter 2002–2003, ISSN 1540-9864. Cached HTML version of a missing PDF file. Retrieved March 10, 2010. The article is based on the book, Inventing Polymer Science: Staudinger, Carothers, and the Emergence of Macromolecular Chemistry by Yasu Furukawa.
Water chemistry analyses are carried out to identify and quantify the chemical components and properties of water samples. The type and sensitivity of the analysis depends on the purpose of the analysis and the anticipated use of the water. Chemical water analysis is carried out on water used in industrial processes, on waste-water stream, on rivers and stream, on rainfall and on the sea. In all cases the results of the analysis provides information that can be used to make decisions or to provide re-assurance that conditions are as expected. The analytical parameters selected are chosen to be appropriate for the decision-making process or to establish acceptable normality. Water chemistry analysis is often the groundwork of studies of water quality, pollution, hydrology and geothermal waters. Analytical methods routinely used can detect and measure all the natural elements and their inorganic compounds and a very wide range of organic chemical species using methods such as gas chromatography and mass spectrometry. In water treatment plants producing drinking water and in some industrial processes using products with distinctive taste and odors, specialized organoleptic methods may be used to detect smells at very low concentrations.
=== Fortification === In the early 1930s, the United States and countries in northern Europe began to fortify milk with vitamin D in an effort to eradicate rickets. This, plus medical advice to expose infants to sunlight, effectively ended the high prevalence of rickets. The proven health benefit of vitamin D led to fortification to many foods, even foods such as hot dogs and beer. In the 1950s, due to some highly publicized cases of hypercalcemia and birth defects, vitamin D fortification became regulated, and even discontinued in some countries. As of 2024, governments have established mandated or voluntary food fortification programs to combat deficiency in, respectively, 15 and 10 countries. Depending on the country, manufactured foods fortified with either D2 or D3 may include dairy milk and other dairy foods, fruit juices and fruit juice drinks, meal replacement food bars, soy-protein–based beverages, wheat flour or corn meal products, infant formulas, breakfast cereals and 'plant milks',.
== Domestic impact == Psychiatrist Thomas Szasz wrote in 1997, "Over the past thirty years, we have replaced the medical-political persecution of illegal sex users ('perverts' and 'psychopaths') with the even more ferocious medical-political persecution of illegal drug users." Assessing from a health perspective, a study in the Annals of Medicine noted: "The U.S. war on drugs has subjected millions to criminalization, incarceration, and lifelong criminal records, disrupting or altogether eliminating their access to adequate resources and supports to live healthy lives."
Sources: en.wikipedia.org
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。
胰岛素释放需要细胞内环腺苷酸与钙信号升高，同时依赖葡萄糖代谢产生的协同信号。血糖水平较低时协同信号不足，分泌增强有限。这一机制在降糖效果与低血糖风险之间提供了缓冲。
白蛋白结合是主要原因，它减少肾小球滤过并保护分子免受蛋白酶降解。序列修饰带来的酶解抵抗同样不可忽略，二者共同作用。脂肪链的疏水性还会影响组织分布，但其对总半衰期的贡献程度仍在研究之中。
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.