This is a working overview of 二肽基肽酶-4, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2025-09-16 and is reviewed periodically as new material appears.
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.
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.
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。
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。
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white lyophilized powder | Batch-to-batch variation is normal |
| Solubility class | Soluble in water, buffer, and dimethyl sulfoxide | Aqueous solubility is moderate |
| Typical storage temperature | Minus 20 degrees Celsius dry, 2 to 8 degrees Celsius reconstituted | Avoid repeated freeze-thaw |
| Common analytical method | Reverse-phase HPLC with electrospray mass detection | Used for purity and mass confirmation |
| Common synonyms | GLP-1 analog, semaglutide peptide | Wording varies across suppliers |
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.
The semaglutide sequence is a 31-residue analogue of human GLP-1, altered at three positions relative to the parent hormone. Aminoisobutyric acid replaces alanine at position 8, arginine replaces lysine at position 34, and a lipophilic diacid is attached to lysine 26 through a short linker. These features are reported consistently in the structural literature. The position 8 substitution blocks recognition by dipeptidyl peptidase-4, while the attached chain drives strong, reversible association with a carrier protein in blood.
Receptor activation raises intracellular cyclic AMP through Gs coupling, which promotes glucose-dependent insulin release and suppresses glucagon secretion when blood glucose is elevated. Effects outside the pancreas include slower gastric emptying and altered appetite signalling in the hypothalamus and hindbrain. The relative contribution of each tissue to overall metabolic outcomes remains an area of active investigation. Central mechanisms in particular are inferred mainly from animal models and indirect human measures rather than direct observation.
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.
The primary target is the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises intracellular cyclic AMP, which potentiates glucose-dependent insulin secretion and lowers glucagon release when blood glucose is elevated. Signalling in the hypothalamus and brainstem is associated with reduced appetite and slower gastric emptying. Because the insulinotropic effect depends on prevailing glucose levels, the hypoglycaemic risk of the peptide alone is described as low in most study settings. The relative contribution of peripheral and central actions remains an active research question.
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
In 2014, Chipotle collaborated on a viral marketing campaign with the rock band Spoon, in support of the band's album, They Want My Soul. For Chipotle's 18th anniversary, the company began wrapping its burritos in gold foil as part of a larger promotion to draw attention to its Food With Integrity mantra. Also as part of the gold foil campaign, Chipotle is offering prizes for customer-created pictures of items wrapped in gold foil. Chipotle hired comedian Amy Sedaris to create a comedic how-to video on wrapping with gold foil, and spread the video using Twitter. In March 2013, Chipotle pulled its sponsorship of a Boy Scouts of America event, citing that organization's ban on LGBT members.
=== No development reported === AB-1224 – microbiome modulator AGX-201 (histamine dihydrochloride salt) – histamine H1 receptor antagonist and histamine H3 receptor agonist Aminolevulinic acid/sodium ferrous citrate (5-ALA-SFC, 5-ALA/SFX; sodium ferrous citrate/aminolevulinic acid; SPP-003) – erythropoiesis stimulant and photosensitizer Aripiprazole transdermal (AQS-1301; transdermal aripiprazole) – dopamine D2 and D3 receptor partial agonist, serotonin 5-HT1A and 5-HT7 receptor partial agonist, serotonin 5-HT2A and 5-HT2B receptor antagonist or inverse agonist, and atypical antipsychotic BAER-101 (AZ-7325; AZD-7325) – selective GABAA α2 and α3 subunit-containing receptor positive allosteric modulator BBP-472 – phosphatidylinositol 3 kinase β (PI3Kβ) inhibitor Fasoracetam co-crystallised (co-crystallised fasoracetam; AEVI-004) – various actions and racetam Guanfacine once-daily (Guanfacine Carrier Wave; SPD-547) – α2-adrenergic receptor agonist KBLP-010 – bacteria replacement and microbiome modulator Oxytocin intranasal (OPN-300; OptiNose oxytocin) – oxytocin receptor agonist Research programme: allosteric modulators - Addex Therapeutics (various) – various actions Research programme: antisense oligonucleotide therapeutics - RogCon U.R (RCUR-313, RCUR-SMP) – voltage-gated sodium channel Nav1.2 expression stimulants Research programme: autism and obesity therapeutics - Berand Neuropharmacology – histone deacetylase inhibitors Research programme: brain development disorder therapeutics - Seaside Therapeutics (STX-110) – metabotropic glutamate mGlu5 receptor antagonists and muscarinic acetylcholine M1 receptor antagonists Research programme: cannabinoid receptor modulators - GW Pharmaceuticals (cannabigerol; CBG) – cannabinoid receptor modulators Research programme: cannabis extract therapeutics - Cannabis Science (CBIS compounds) – cannabinoid receptor modulators Research programme: central nervous system therapeutics - AbbVie/Rugen – undefined mechanism of action Research programme: CNS disorder therapeutics - Promentis Pharmaceuticals – antioxidants, glutamate receptor modulators, SLC7A11 modulators Research programme: CNS disorders therapeutics - Sage Therapeutics (SAGE-105; SGE-202; SGE-301; SGE-516) – GABAA receptor modulators and ionotropic glutamate NMDA receptor modulators Research programme: G protein-coupled receptor modulating small molecules - Omeros Corporation – G protein-coupled receptor modulator and neuromedin U receptor modulator Research programme: GPCR modulators - Nxera Pharma – various actions Research programme: immunomodulating bacteria-based therapeutics - 4D Pharma – bacteria replacements Research programme: metabotropic glutamate receptor 5 antagonists - Roche/Seaside Therapeutics – metabotropic glutamate mGlu5 receptor antagonists Research programme: oxytocin intranasal - Pastorus Pharma – neurotransmitter modulators/oxytocin receptor agonists Research programme: therapeutic autoantibodies - Sengenics – undefined mechanism of action RG-7713 (RG7713) – vasopressin V1A receptor antagonist Tideglusib (AMO-02, NP-031112, NP-12; Nypta, Zentylor) – glycogen synthase kinase 3β (GSK-3β) inhibitor Vafidemstat (ORY-2001) – dual lysine specific demethylase 1 (LSD1) inhibitor and monoamine oxidase B (MAO-B) inhibitor Xenon (NBTX-001) – ionotropic glutamate NMDA receptor antagonist
== Natural and synthetic cannabinoids == The following are banned for in-competition use only, with the exception of cannabidiol (CBD) which is not banned for any use. In 2013, the level of THC metabolite allowed was changed from 15 ng/mL to 150 ng/mL so as to only detect in-competition use.
Sources: en.wikipedia.org
==== Louis Vuitton fashion shows ==== Williams was hand-selected to be the new creative director of menswear at luxury fashion house Louis Vuitton in 2023. In a story with the New York Times about the job and his upcoming debut fashion show with the brand, an unheard song with Pusha T ("Chains & Whips") was teased, although it was not yet revealed as a Clipse song. The three annual spring–summer shows from this point until Let God Sort Em Out's release all featured new Clipse music in their soundtracks, along with other songs. "Chains & Whips" was debuted at the Louis Vuitton's Men's Spring–Summer Show 2024 on June 20, 2023, although Kendrick Lamar's guest verse was not yet included. Pusha T and Malice also walked on the runway in Williams's designs. For the Men's Spring–Summer Show 2025 on June 18, 2024, "The Birds Don't Sing" was previewed for the first time, featuring vocals by John Legend. The Men's Spring–Summer Show 2026 debuted "So Be It Pt. II" on June 24, 2025.
Benninghoven graduated from the University of Cologne in 1961 where he worked with Fritz Kirchner (1896–1967) and completed his habilitation in surface physics in Cologne two years later. He first worked as professor in Cologne from 1965 to 1973 until he moved to a full professor position in experimental physics at the University of Münster in 1972. He worked on static secondary ion mass spectrometry (SIMS) and its applications, and developed SIMS instruments. In 1989 he co-founded IonTOF, a company that became a world-leader in TOF-SIMS instrumentation. He has written over 300 scientific articles and several books on the topic of SIMS, many of which have become reference works on SIMS. For his work, he has received the Technology Transfer prize (German Ministry of Education and Research) and the 1984 Gaede-Langmuir Prize (American Vacuum Society) for the development of concepts and instrumentation in static secondary ion mass spectrometry and the demonstration of its usefulness in manifold applications. In 1990 he shared the Fritz-Pregl-Medaille of the Austrian Society of Analytical Chemistry with Wilhelm Simon. From 1977 to 1983, he was president of the German Vacuum Society (part of the German Physical Society).
Potassium-40 is especially important in potassium–argon (K–Ar) dating. Argon is a gas that does not ordinarily combine with other elements. So, when a mineral forms – whether from molten rock, or from substances dissolved in water – it will be initially argon-free, even if there is some argon in the liquid. However, if the mineral contains traces of potassium, then decay of the 40K isotope present will create fresh argon-40 that will remain locked up in the mineral. Since the rate at which this conversion occurs is known, it is possible to determine the elapsed time since the mineral formed by measuring the ratio of 40K and 40Ar atoms contained in it. The argon in Earth's atmosphere is 99.6% 40Ar, but the argon in the Sun – and presumably in the primordial material that condensed into the planets – is mostly 36Ar, with less than 15% of 38Ar. It follows that most of Earth's argon derives from potassium-40 that decayed into argon-40, which eventually escaped to the atmosphere.
== History == Insulin was first used as a medication in Canada by Charles Best and Frederick Banting in 1922. This is a chronology of key milestones in the history of the medical use of insulin. For more details on the discovery, extraction, purification, clinical use, and synthesis of insulin, see Insulin
Sources: en.wikipedia.org
=== Biocompatibility, biodegradability, and biodistribution === One major concern with any form of drug delivery system, including nanogels, is potential side effects and damage to healthy tissue in addition to causing a negative immune response with the introduction of a foreign substance. This has to be balanced with the need for nanogels to remain within circulation for an adequate period to deliver cargo and produce a therapeutic effect. To combat a significant immune response, degradable nanogels are the typical default since they are considered less toxic compared to non degradable nanogels. The compliance and small size of degradable nanogels also allows them to travel through blood vessels and reach their target area before consumption by immune cells or filtration by the liver and spleen.
== Organismal involvement == This enzyme is widely distributed and a number of crystal structures have been solved, including in Escherichia coli, Pyrococcus Horikoshii, Thermoplasma acidophil, Homo sapiens, Thermus thermophilus and Mycobacterium tuberculosis. The most extensive structural studies have been done in E. coli.
Many of the opposition groups subsequently began competing for influence in the power vacuum that followed the ouster of Barre's regime. In the south, armed factions led by USC commanders General Mohamed Farah Aidid and Ali Mahdi Mohamed, in particular, clashed as each sought to exert authority over the capital. In 1991, a multi-phased international conference on Somalia was held in neighbouring Djibouti. Owing to the legitimacy bestowed on Muhammad by the Djibouti conference, he was subsequently recognised by the international community as the new President of Somalia. He was not able to exert his authority beyond parts of the capital. Power was instead vied with other faction leaders in the southern half of Somalia and with autonomous sub-national entities in the north. The Djibouti conference was followed by two abortive agreements for national reconciliation and disarmament, which were signed by 15 political stakeholders: an agreement to hold an Informal Preparatory Meeting on National Reconciliation, and the 1993 Addis Ababa Agreement made at the Conference on National Reconciliation. In 1998, the state of Puntland was established under the leadership of Abdullahi Yusuf, head of the Somali Salvation Democratic Front. In the early 1990s, due to the protracted lack of a permanent central authority, Somalia began to be characterised as a "failed state". Following the collapse of the Somali Democratic Republic in early 1991, a new phenomenon emerged – the establishment of Sharia courts to impose law and order on the volatile neighborhoods of Mogadishu.
E. × cantabrigiense Stearn, hybrid between E. alpinum and E. pubigerum E. × perralchicum Stearn, hybrid between E. perralderianum and E. pinnatum subsp. colchicum E. × rubrum Morr., hybrid between E. alpinum and E. grandiflorum E. × versicolor Morr., hybrid between E. grandiflorum and E. pinnatum subsp. colchicum E. × warleyense Stearn, hybrid between E. alpinum and E. pinnatum subsp. colchicum E. × youngianum Fisch & C.A.Mey, hybrid between E. diphyllum and E. grandiflorum
=== Long-term use === Osteoporosis and bone fracture have been observed in people on high-dose and/or long-term (over one year) prescription proton pump inhibitors. Hypomagnesia has been observed in people on medications like pantoprazole when taken for longer periods of time (generally one year or more, although cases have been reported with regimens as short as three months). Deficiencies such as vitamin B12 deficiency, iron deficiency, and calcium deficiency may be seen with long term use. Vitamin B12 deficiency is due to the change in the acidic environment within the stomach with the use of pantoprazole which prevents peptidases from being activated. This prevents the cleaving of R-factor from vitamin B12 and prevents its absorption. Rebound hypergastrinemia may be seen when stopping the medication after long term use.
Sources: en.wikipedia.org
Manufacturers commonly state multi-year stability when the powder is kept dry and frozen. Actual shelf life depends on residual moisture, vial sealing, and storage temperature. A re-test by chromatography is the only way to confirm remaining purity.
Deamidated and oxidized forms are the most frequently reported impurities. Truncated peptide fragments from incomplete synthesis also appear at low levels. Their relative abundance grows with time, heat exposure, and unfavorable pH.
Retention time matching on a validated column provides strong circumstantial evidence. It does not distinguish compounds with similar hydrophobicity. Mass measurement or peptide mapping is needed for unambiguous identification.
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。