This is a working overview of deamidation, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2025-09-18 and is reviewed periodically as new material appears.
定量分析的主流方法是反相高效液相色谱联用紫外或质谱检测，利用肽在疏水固定相上的保留行为确定纯度与含量。对于生物基质中的浓度测定，常采用液相色谱串联质谱，并配合固相萃取或蛋白沉淀进行样品前处理。免疫分析法也可使用，但可能受到结构相关肽的交叉反应干扰。
纯度评估通常综合反相色谱、体积排阻色谱与质谱三方面信息：前者反映疏水性杂质，后者反映聚集体，质谱则确认分子量与主要降解产物。有关降解途径的完整图谱——例如脱酰胺、氧化与水解各占多大比例——在不同储存条件下仍有差异，属于需要逐案验证的问题。
At the receptor level, tirzepatide activates both the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. Both belong to the class B family of G protein-coupled receptors and signal largely through cyclic AMP accumulation. The compound binds the two receptors with differing affinity, and the pattern of signaling at each site is described in the literature as biased rather than simply proportional to occupancy. Tissues carrying these receptors include pancreatic islets, adipose tissue, the central nervous system, and the gastrointestinal tract. The relative weight of each receptor population in producing metabolic effects continues to be studied.
Published work supports the view that engaging two incretin receptors produces changes in glucose handling and body weight larger than those seen with single-receptor activation. Why that difference arises is not fully settled. Open questions include how much of the observed weight effect depends on central versus peripheral signaling, and whether the two receptors form interacting complexes. Most reported findings come from controlled trials and animal models, and translation between species is imperfect. Further research is expected to refine these points over time.
Tirzepatide is a synthetic peptide built from 39 amino acid residues. Its sequence is related to human glucose-dependent insulinotropic polypeptide, with modifications that include a C-terminal extension and a C20 fatty diacid joined through a linker. Those changes raise the molecule's affinity for serum albumin, which slows renal filtration and lengthens the time it stays in circulation. The free base has an average molecular mass near 4813.5 daltons. The compound is made by solid-phase peptide synthesis followed by chromatographic purification.
| Property | Value | Notes |
|---|---|---|
| 储存温度 | 2 至 8 摄氏度 | 固体粉末，避光密封 |
| 外观 | 白色至类白色冻干粉 | 溶解后为澄清至微乳光 |
| 溶解性 | 易溶于水性缓冲液 | 避免剧烈振荡 |
| 常规纯度方法 | 反相高效液相色谱 | 紫外或质谱检测 |
| 定量方法 | 液相色谱串联质谱 | 配合固相萃取前处理 |
Research and analytical settings increasingly require documentation of peptide origin and chain of custody. Certificate of analysis documents typically report purity by chromatographic area, mass confirmation, appearance, and residual solvent or counterion content. Independent verification by an accredited laboratory is common when a material will be used in a regulated study. Open questions remain about how well compendial methods transfer between laboratories, and about which impurity thresholds are meaningful for materials not intended for clinical use.
Peptide-based pharmaceutical products such as tirzepatide require controlled temperature management to preserve structural integrity. Manufacturer labeling generally specifies refrigeration at 2 to 8 degrees Celsius before first use, with protection from light and freezing. Exposure to repeated temperature cycling can promote aggregation or deamidation, which alters the analytical profile even when the visible solution appears unchanged. Once a product is in use, the permitted storage window and temperature range are defined by the specific labeled presentation rather than by general peptide rules.
Identity and purity assessment of tirzepatide relies primarily on reversed-phase high-performance liquid chromatography coupled with ultraviolet detection. Mass spectrometry, often in electrospray ionization mode, confirms the molecular mass and detects sequence-related impurities. Peptide mapping after enzymatic digestion provides residue-level confirmation of the backbone. Each method addresses a different question: chromatography for purity and related substances, mass measurement for identity, and mapping for sequence fidelity. No single technique covers all three.
After subcutaneous injection, absorption is gradual, and peak plasma levels are generally reached within one to three days. Albumin binding extends the apparent half-life to roughly five days, which supports a weekly administration schedule. Metabolism proceeds mainly through proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid chain, rather than through cytochrome P450 pathways. Eliminated fragments are largely recycled through general protein turnover, and excretion of intact drug in urine is minimal. These properties distinguish the molecule from short-acting incretin mimetics.
Tirzepatide is a synthetic peptide of 39 amino acids engineered from the native glucose-dependent insulinotropic polypeptide sequence. Its structure incorporates several non-natural residues and a C-terminal segment derived from glucagon-like peptide-1, together with a C20 fatty diacid moiety attached through a linker. The lipophilic side chain promotes binding to serum albumin, which slows renal clearance after administration. The compound is classified as a dual incretin receptor agonist and is supplied as a lyophilized powder for reconstitution or as a preformulated solution, depending on the presentation.
Reported outcomes in large trials include dose-dependent weight reduction and improvements in glycemic markers over periods ranging from several months to more than a year. Whether the compound alters long-term cardiovascular or renal outcomes is being examined in dedicated outcome studies, so those questions remain open. Labeling describes gastrointestinal effects such as nausea and diarrhea, which tend to appear during dose escalation. Discontinuation rates and the durability of effects after treatment stops vary across study populations and are still debated.
Tirzepatide is a synthetic peptide developed as a dual agonist at the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. Its structure is built on a GIP-derived backbone with non-natural amino acid substitutions and a fatty diacid side chain that promotes albumin binding and slows clearance. That modification supports once-weekly subcutaneous dosing. Registrational trial programs reported reductions in body weight and glycated hemoglobin alongside the drug's glycemic effects.
Both receptors are class B G protein-coupled receptors that signal largely through Gs-mediated cyclic AMP production. Activation within pancreatic islets increases glucose-dependent insulin secretion and suppresses glucagon release when glucose is elevated. Outside the pancreas, signaling in the central nervous system and gut appears to influence appetite and gastric emptying. The relative contribution of each receptor to observed clinical effects remains under investigation, and the two pathways are not simply additive in practice.
Degradation pathways for tirzepatide include deamidation, oxidation, and aggregation, which are common for therapeutic peptides. These processes can be monitored by size-exclusion chromatography (SEC) for aggregates and ion-exchange chromatography for charge variants. Forced degradation studies under acidic, basic, oxidative, and thermal stress help identify potential impurities. The exact stability profile depends on formulation, concentration, and container-closure system.
Analytical characterization of tirzepatide typically employs reversed-phase high-performance liquid chromatography (RP-HPLC) for purity assessment and peptide mapping. Mass spectrometry, often coupled with electrospray ionization, confirms molecular weight and sequence integrity. Amino acid analysis and capillary electrophoresis may also be used to detect impurities or degradation products. These methods are essential for batch release and stability studies.
Storage recommendations for tirzepatide generally specify refrigeration at 2–8 °C to maintain stability. The peptide should be protected from light and kept in its original packaging to prevent aggregation or adsorption. Freezing is not recommended because freeze-thaw cycles can cause aggregation or precipitation. Once dispensed, storage conditions and in-use periods follow product-specific labeling, which may allow room temperature storage for a limited time.
Seven genes encode seven distinct 14-3-3 proteins in most mammals (See Human genes below) and 13–15 genes in many higher plants, though typically in fungi they are present only in pairs. Protists have at least one. Eukaryotes can tolerate the loss of a single 14-3-3 gene if multiple genes are expressed, but deletion of all 14-3-3s (as experimentally determined in yeast) results in death. 14-3-3 proteins are structurally similar to the Tetratrico Peptide Repeat (TPR) superfamily, which generally have 9 or 10 alpha helices, and usually form homo- and/or hetero-dimer interactions along their amino-termini helices. These proteins contain a number of known common modification domains, including regions for divalent cation interaction, phosphorylation & acetylation, and proteolytic cleavage, among others established and predicted. 14-3-3 binds to peptides. There are common recognition motifs for 14-3-3 proteins that contain a phosphorylated serine or threonine residue, although binding to non-phosphorylated ligands has also been reported. This interaction occurs along a so-called binding groove or cleft that is amphipathic in nature. To date, the crystal structures of six classes of these proteins have been resolved and deposited in the public domain.
Transmembrane protein 125 is a protein that, in humans, is encoded by the TMEM125 gene. It has 4 transmembrane domains and is expressed in the lungs, thyroid, pancreas, intestines, spinal cord, and brain. Though its function is currently poorly understood by the scientific community, research indicates it may be involved in colorectal and lung cancer networks. Additionally, it was identified as a cell adhesion molecule in oligodendrocytes, suggesting it may play a role in neuron myelination. The TMEM125 gene has no aliases, except for its encoded protein’s name. Its cytogenic location is at 1p34.2 on the plus strand and it spans from bases 43,272,723 to 43,273,379. TMEM125 comprises four exons. Five TMEM125 promoters were identified by Genomatix Gene2Promoter. The primary promoter (NM_001320244) is 1881 bp in length. It consists of binding sites for fork head domain factors and zinc finger transcription factors.
=== Industrial and chemical === Technetium-99 decays almost entirely by beta decay, emitting beta particles with consistent low energies and no accompanying gamma rays. Moreover, its long half-life means that this emission decreases very slowly with time. It can also be extracted to a high chemical and isotopic purity from radioactive waste. For these reasons, it is a U.S. National Institute of Standards and Technology (NIST) standard beta emitter, and is used for equipment calibration. Technetium-99 has also been proposed for optoelectronic devices and nanoscale nuclear batteries. Like rhenium and palladium, technetium can serve as a catalyst. In processes such as the dehydrogenation of isopropyl alcohol, it is a far more effective catalyst than either rhenium or palladium. However, its radioactivity is a major problem in safe catalytic applications. When steel is immersed in water, adding a small concentration (55 ppm) of potassium pertechnetate(VII) to the water protects the steel from corrosion, even if the temperature is raised to 250 °C (523 K). For this reason, pertechnetate has been used as an anodic corrosion inhibitor for steel, although technetium's radioactivity poses problems that limit this application to self-contained systems. While (for example) CrO2−4 can also inhibit corrosion, it requires a concentration ten times as high. In one experiment, a specimen of carbon steel was kept in an aqueous solution of pertechnetate for 20 years and was still uncorroded.
=== Mechanism of action === Insulin degludec is an ultra-long acting insulin that, unlike insulin glargine, is active at a physiologic pH. The addition of hexadecanedioic acid via an amide linkage to lysine at the B29 position allows for the formation of multi-hexamers in subcutaneous tissues. This allows for the formation of a subcutaneous depot that results in slow insulin release into the systemic circulation.
Sources: en.wikipedia.org
At anesthetic doses, 10–20% of adults and 1–2% of children experience adverse psychiatric reactions that occur during emergence from anesthesia, ranging from dreams and dysphoria to hallucinations and emergence delirium. Psychotomimetic effects decrease when adding lamotrigine and nimodipine and can be counteracted by pretreatment with a benzodiazepine or propofol. Ketamine anesthesia commonly causes tonic-clonic movements (greater than 10% of people) and rarely hypertonia. Vomiting can be expected in 5–15% of the patients; pretreatment with propofol mitigates it as well. Laryngospasm occurs only rarely with ketamine. Ketamine, generally, stimulates breathing; however, in the first 2–3 minutes of a high-dose rapid intravenous injection, it may cause a transient respiratory depression. At lower sub-anesthetic doses, psychiatric side effects are prominent. The most common psychiatric side effects are dissociation, visual distortions, and numbness. Also common (20–50%) are difficulty speaking, confusion, euphoria, drowsiness, and difficulty concentrating. Hallucinations are described by 6–10% of people. Dizziness, blurred vision, dry mouth, hypertension, nausea, increased or decreased body temperature, or flushing are the common (>10%) non-psychiatric side effects. All these adverse effects are most pronounced by the end of the injection, dramatically reduced 40 minutes afterward, and completely disappear within 4 hours after the injection.
Calcitriol also reduces calcium loss to urine. Per the diagram, calcitriol suppresses the parathyroid hormone gene, thus creating a negative feedback loop that combines to tightly maintain plasma calcium in a normal range of 2.1-2.6 mmol/L for total calcium and 1.1-1.3 mmol/L for ionized calcium. However, there are also vitamin D receptors in bone cells, so that with serum vitamin D in great excess, osteoclastic bone resorption is promoted regardless of PTH, resulting in hypercalcemia and its symptomology.
==== NATO involvement ==== The North Atlantic Treaty Organization (NATO) has played a role in addressing the issue of drug trafficking, particularly in Afghanistan, as part of its broader security and stabilization efforts. NATO has supported counter-narcotics initiatives by assisting the Afghan government in building its capacity to combat the illegal drug trade, which is seen as a major source of funding for insurgent groups. NATO's efforts include training and equipping Afghan security forces to enhance their ability to disrupt drug trafficking networks, as well as supporting intelligence-sharing and coordination with international partners. These activities are framed within NATO's mission to promote stability and security, recognizing the link between the drug trade and threats to regional and global security. However, perspectives on NATO's involvement in counter-narcotics operations have varied, with some reports highlighting tensions with other international actors, such as the United Nations. While NATO emphasizes its contributions to reducing the drug trade through capacity-building and support for Afghan-led initiatives, other sources have noted discrepancies in reported outcomes, suggesting that the drug trade in Afghanistan remained robust despite these efforts. For instance, data from 2012 indicates that opium production continued to thrive, raising questions about the effectiveness of NATO's strategies in this domain.
In the 1950s, Alfred Nier developed the technique of ID-TIMS, which later become the first tool used in monazite geochronology. Since this method involves the chemical separation of monazite (isotope dilution), it is regarded as a conventional analysis technique. Generally, it takes several hours for a U-Pb measurement. The precision of date is nearly 0.1%, provided that the ages are concordant (i.e. not dates reflecting mixing of zonations). It is regarded as the most precise method in monazite geochronology. Monazite mineral grains are carefully hand-picked for dating. They are spiked with a tracer solution and dissolved in HF or HCl. Using ion exchange chemistry, U, Th and Pb are separated from other elements. The purposes of the separation are (1) potential isobaric interference should be removed before analysis because of the high-sensitivity and low-mass resolution nature of TIMS; (2) ionization of the elements of interest maybe impeded by other elements, which results in reduced signal size and precision. The separated U, Th and Pb samples are put carefully onto a metal filament, which is usually made from Re. The elements are heated and ionize to their respective ions, which are accelerated under a strong magnetic field and are measured by a detector. The tracer solution is a solution with a known amount of U and Pb tracer isotopes. Due to elemental fractionation, both elements cannot be measured simultaneously by TIMS. The tracer solution is therefore used to measure ratios of sample isotope to tracer isotopes.
The Hungarian Revolution of 1956 occurred shortly after Khrushchev arranged the removal of Hungary's Stalinist leader Mátyás Rákosi. In response to a popular anti-communist uprising, the new regime formally disbanded the secret police, declared its intention to withdraw from the Warsaw Pact and pledged to re-establish free elections. The Soviet Army invaded. Thousands of Hungarians were killed and arrested, imprisoned and deported to the Soviet Union, and approximately 200,000 Hungarians fled Hungary. Hungarian leader Imre Nagy and others were executed following secret trials. From 1957 through 1961, Khrushchev openly and repeatedly threatened the West with nuclear annihilation. He claimed that Soviet missile capabilities were far superior to those of the United States, capable of wiping out any American or European city. According to John Lewis Gaddis, Khrushchev rejected Stalin's "belief in the inevitability of war," however. The new leader declared his ultimate goal was "peaceful coexistence". In Khrushchev's formulation, peace would allow capitalism to collapse on its own, as well as giving the Soviets time to boost their military capabilities, which remained for decades until Gorbachev's later "new thinking" envisioning peaceful coexistence as an end in itself rather than a form of class struggle. The events in Hungary produced ideological fractures within the communist parties of the world, particularly in Western Europe, with great decline in membership, as many in both western and socialist countries felt disillusioned by the brutal Soviet response.
Sources: en.wikipedia.org
=== Alternative protein sources === With the global population expected to reach 9.7 billion by 2050, there is an urgent need for alternative protein sources that are sustainable, nutritious, and environmentally friendly. Plant-based proteins are gaining popularity as they require fewer resources and produce fewer greenhouse gas emissions compared to animal-based proteins. Companies like Beyond Meat and Impossible Foods have developed plant-based meat alternatives that mimic the taste and texture of traditional meat products.
Global Navigation Satellite System (GNSS) or satnav system – A system of satellites which allows geographical location on Earth (latitude, longitude, and altitude/elevation) to be determined to high precision (within a few metres) by small portable navigation instruments, by timing the arrival of radio signals from the satellites. These are the most widely used navigation systems today. The main satellite navigation systems are the US Global Positioning System (GPS), Russia's GLONASS, China's BeiDou Navigation Satellite System (BDS) and the European Union's Galileo.
reverse genetics An experimental approach in molecular genetics in which a researcher starts with a known gene and attempts to determine its function or its effect on phenotype by any of a variety of laboratory techniques, commonly by deliberately mutating the gene's DNA sequence or by repressing or silencing its expression and then screening the mutant organisms for changes in phenotype. When the gene of interest is the only one in the genome whose expression has been manipulated, any observed phenotypic changes are assumed to be influenced by it. This is the opposite of forward genetics, in which a known phenotype is linked to one or more unknown genes.
Sharypova said she went to take a shower, during which Zverev continued berating her from outside the bathroom door. "When I got out of the shower, I was starting to take a towel and he came and said, 'Pack your stuff right now and leave,'" Sharypova recalled. "I'm just like, 'OK, can you wait a few minutes please? I'm naked here.'" From there, Sharypova said, Zverev attacked her more violently than he ever had before. She said that he grabbed her by the throat and pushed her up against the hard tile wall of the bathroom. "He started to punch me, and this time I understand that I can't be dough for punching," she said. Rothenberg reports that "Sharypova has repeatedly said that she is not interested in pursuing criminal or civil action against Zverev." She told Rothenberg she wanted to be open and honest to help other women who tend to stay silent in such situations due to fear of not being believed. Zverev secured an injunction from a Berlin court against Slate later in August 2021, barring it from publishing the assault allegations without stronger evidence. In response, Slate stated that it stands by the reporting in the article and has not removed the article from its website. They protested that the injunction was obtained without the organization having an opportunity to present evidence, and they appealed the decision. Commentator Mary Carillo stepped down from her presenting role at the 2021 Laver Cup in response to the ATP's handling of the allegations.
Historically, patients of frontal lobotomy were, immediately following surgery, often stuporous and incontinent. Some developed an enormous appetite and gained considerable weight. Seizures were another common complication of surgery. Emphasis was put on the training of patients in the weeks and months following surgery. The purpose of the operation was to reduce the symptoms of mental disorders, and it was recognized that this was accomplished at the expense of a person's personality and intellect. British psychiatrist Maurice Partridge, who conducted a follow-up study of 300 patients, said the treatment achieved its effects by "reducing the complexity of psychic life". Following the operation, spontaneity, responsiveness, self-awareness, and self-control were reduced. Activity was replaced by inertia, and people were mostly left emotionally blunted and restricted in their intellectual range. The consequences of the operation have been described as "mixed". However, many lobotomy patients suffered devastating postoperative complications, including intracranial hemorrhage, epilepsy, alterations in affect and personality, brain abscess, dementia, and death. Ominous portrayals of lobotomized patients in novels, plays, and films further diminished public opinion, and the development of antipsychotic medications led to a rapid decline in lobotomy's popularity and Walter Freeman's reputation. Others could leave the hospital or become more manageable within the hospital.
Sources: en.wikipedia.org
建议在低温、避光、干燥环境中密封保存，常见条件为 2 至 8 摄氏度，长期存放可置于更低温度。应避免反复冻融，并尽量减少容器开启次数。
溶解后的稳定时间通常短于固体形态，受浓度、缓冲液和容器材质影响。冷藏条件下一般只能维持较短时间，具体期限应通过实际稳定性实验确认。
反相高效液相色谱用于纯度与含量测定，液相色谱串联质谱用于生物基质中的定量，体积排阻色谱用于检测聚集体。多种方法结合才能较完整地表征样品。
It is a synthetic peptide and a dual agonist of two incretin receptors. It is not a small molecule, and it is not structurally related to the older single-receptor peptide agonists.