If you have been reading about 非天然氨基酸 and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-07-21. Where a claim depends on a specific study, the study is described rather than over-claimed.
Ipamorelin 是一种合成五肽，序列为 Aib-His-D-2-Nal-D-Phe-Lys-NH2，分子式 C38H49N9O5，游离碱分子量约 711.85 g/mol。它属于生长激素促分泌素（GHS）家族，作用靶点是胃饥饿素受体 GHS-R1a。该化合物由诺和诺德的研究团队在二十世纪九十年代末报道，设计目标是提高对生长激素释放的选择性。C 端酰胺化与 N 端 Aib 残基是两个用于抵抗肽酶降解的结构特征。
在 GHS 家族中，早期肽类如 GHRP-6 与 GHRP-2 会同时促进生长激素、皮质醇与催乳素的释放，并明显增加食欲。Ipamorelin 在动物与早期人体研究中表现出对生长激素释放的相对选择性，对上述其他激素的影响较小。这种差异通常归因于受体结合模式与下游信号偏向的不同，而完整的分子解释仍有待补充。需要区分的是，选择性是研究观察中的相对程度，并非绝对界限。
从用途定位看，ipamorelin 目前主要以研究用肽的身份被讨论，未见主要药品监管机构将其批准为治疗药物。市售材料通常标注仅供研究使用，不得用于人体或诊断程序。文献中它常与生长激素促分泌素、GHS-R1a 激动剂、胃饥饿素拟似物等表述并列出现。既有研究的样本量普遍偏小，因此对其效应强度与一致性的描述应保持谨慎。
Signal transduction begins when the peptide binds GHSR-1a on pituitary somatotrophs. The receptor couples to Gq/11 proteins, activating phospholipase C, which cleaves phosphatidylinositol bisphosphate into inositol trisphosphate and diacylglycerol. Inositol trisphosphate releases calcium from intracellular stores, and the resulting rise in cytosolic calcium drives growth hormone vesicle fusion. Concurrent Gs coupling and cyclic AMP elevation have also been reported, and the relative contribution of each arm to the overall secretory response is not fully settled.
Structural features distinguish the molecule from earlier secretagogues. An alpha-aminoisobutyric acid residue near the N-terminus and a D-naphthylalanine substitution increase receptor affinity, while C-terminal amidation improves resistance to exopeptidases. These modifications are associated with reduced stimulation of appetite and of the hypothalamic-pituitary-adrenal axis compared with hexarelin or growth hormone releasing peptide-6. Whether the same profile applies at every dose level studied is a matter of ongoing investigation rather than settled consensus.
| Property | Value | Notes |
|---|---|---|
| 分子式 | C38H49N9O5 | 五肽，C 端酰胺化 |
| 分子量 | 约 711.85 g/mol | 游离碱形式 |
| 外观 | 白色至类白色冻干粉 | 研究用材料的常见形态 |
| 溶解性 | 溶于水及 DMSO 等极性溶剂 | 建议现配现用 |
| 储存温度 | -20 °C 或更低 | 干燥、避光、限制冻融次数 |
Purity is normally reported as a percentage of total peak area, a figure that does not account for water content, residual solvents, or counterions. Trifluoroacetate and acetate are the most frequent counterions in lyophilized peptides, and they shift the true peptide content away from the mass of the powder. A separate quantitative assay is therefore needed to state content accurately. Certificates of analysis often omit these details, which makes batch-to-batch comparison difficult and limits conclusions drawn when results from different suppliers are compared.
Lyophilized material is generally held at minus twenty degrees Celsius or lower, protected from moisture and light. Repeated excursions to room temperature cause condensation inside the vial and gradual moisture uptake, both of which shorten shelf life. Containers should be allowed to equilibrate before opening so that water does not condense on the solid. Dividing a batch into single-use aliquots reduces freeze-thaw cycling. Solid peptide handled this way is usually considered stable for months to years, while the same material in solution degrades on a much shorter timescale.
Common solvents for laboratory work include water, buffered saline, and dimethyl sulfoxide. Once dissolved, the peptide is exposed to hydrolysis and oxidation, and alkaline conditions accelerate breakdown. Low-binding plasticware and the addition of a carrier protein reduce losses to container surfaces, which can otherwise be substantial at low concentrations. Solutions are typically kept cold and used within days. Investigators working with the compound generally prepare fresh working dilutions rather than storing dilute stocks, and they avoid repeated warming of the same vial.
Mass spectrometry confirms identity and reveals structural deviations that chromatography alone can miss. Positive-mode electrospray ionisation generally yields multiply charged ions whose deconvoluted mass is checked against the theoretical value. Amino acid analysis, and enzymatic digestion with subsequent fragment mapping, provide independent confirmation of sequence and of the terminal amide. Analysts take care to separate the target from deletion sequences, which may differ by one residue and therefore by only a small mass increment.
The lyophilised solid is normally held at -20 °C or colder, shielded from light and moisture. Stability in that state is measured in years, although shelf life depends on residual water content and the container seal. Once dissolved, the peptide is more fragile: aqueous solutions are commonly kept at 2-8 °C and used within days to weeks, and repeated freeze-thaw cycling is avoided. Strongly acidic or basic conditions accelerate hydrolysis, and prolonged exposure to them can strip the terminal amide.
Purity assessment for this peptide relies mainly on reversed-phase high-performance liquid chromatography. A C18 column with a water-acetonitrile gradient containing trifluoroacetic acid separates the target from truncated sequences and oxidation products. Detection near 214 nm exploits the amide backbone, while the aromatic side chains allow additional monitoring close to 280 nm. Reported purity values depend on the method, so a certificate of analysis carries weight only when gradient, column and integration parameters are given.
Ipamorelin is a synthetic pentapeptide that belongs to the growth hormone secretagogue class of compounds. Its sequence is Aib-His-D-2-Nal-D-Phe-Lys-NH2, a structure that differs from natural ghrelin in length and in the presence of non-natural amino acid residues. Early laboratory work described it as a comparatively selective agent that stimulates growth hormone release with limited effect on other pituitary hormones. The compound is supplied as a lyophilized solid for research use and has no identified natural source in the body.
Activity is mediated mainly through the growth hormone secretagogue receptor, now generally called the ghrelin receptor or GHS-R1a. Binding at this G-protein-coupled receptor triggers phospholipase C signaling, calcium mobilization, and release of growth hormone from pituitary somatotrophs. Reports describe less pronounced stimulation of adrenocorticotropic hormone and prolactin compared with earlier secretagogues such as hexarelin or GHRP-6. Selectivity figures vary between assay systems, so the degree of separation from other secretagogues is an area of ongoing comparison rather than a fixed constant.
In animal and early human studies, ipamorelin produces pulsatile growth hormone release and a secondary rise in insulin-like growth factor 1. The magnitude and duration of that rise depend on route, sampling schedule, and the baseline endocrine state of the subject. Whether repeated exposure alters the response over time is not firmly settled, since some reports describe stable pulsatility while others note attenuation. Most published data come from small samples, which limits the strength of any general claim about long-term behavior.
=== Bogorad's syndrome === Bogorad's syndrome, also known as "crocodile tears syndrome", is an uncommon consequence of nerve regeneration subsequent to Bell's palsy or other damage to the facial nerve. Efferent fibers from the superior salivary nucleus become improperly connected to nerve axons projecting to the lacrimal glands, causing one to shed tears (lacrimate) on the side of the palsy during salivation while smelling foods or eating. It is presumed that this would cause salivation while crying due to the inverse improper connection of the lacrimal nucleus to the salivary glands, but this would be less noticeable. The condition was first described in 1926 by its namesake, Russian neuropathologist F. A. Bogorad, in an article titled "Syndrome of the Crocodile Tears" (alternatively, "The Symptom of the Crocodile Tears") that argued the tears were caused by the act of salivation.
In 1941, at age 40, Pauling was diagnosed with Bright's disease, a renal disease. Following the recommendations of Thomas Addis, who actively recruited Ava Helen Pauling as "nutritionist, cook, and eventually as deputy 'doctor'", Pauling believed he was able to control the disease with Addis's then-unusual low-protein salt-free diet and vitamin supplements. Thus Pauling's initial – and intensely personal – exposure to the idea of treating disease with vitamin supplements was positive. In 1965, Pauling read Niacin Therapy in Psychiatry by Abram Hoffer and theorized vitamins might have important biochemical effects unrelated to their prevention of associated deficiency diseases. In 1968, Pauling published a brief paper in Science entitled "Orthomolecular psychiatry", giving a name to the popular but controversial megavitamin therapy movement of the 1970s, and advocating that "orthomolecular therapy, the provision for the individual person of the optimum concentrations of important normal constituents of the brain, may be the preferred treatment for many mentally ill patients." Pauling coined the term "orthomolecular" to refer to the practice of varying the concentration of substances normally present in the body to prevent and treat disease. His ideas formed the basis of orthomolecular medicine, which is not generally practiced by conventional medical professionals and has been strongly criticized. In 1973, with Arthur B.
On March 10, 2014, the first Dunkin' Donuts/Baskin-Robbins combination store in Southern California opened in Ramona. This is Dunkin' Donuts' third California shop to open, following shops in Barstow and on Camp Pendleton. Since March 2014, Dunkin' Donuts has opened several additional locations throughout California, including the Los Angeles area. Dunkin' Donuts shops opened in the San Francisco Bay Area in Walnut Creek, Half Moon Bay, and American Canyon in 2016, as well as South San Francisco and Fremont, in 2017.
The Marxist-Leninist leadership of the Soviet Union intensely debated foreign policy issues and changed directions several times. Even after Stalin assumed dictatorial control in the late 1920s, there were debates, and he frequently changed positions. During the country's early period, it was assumed that Communist revolutions would break out soon in every major industrial country, and it was the Russian responsibility to assist them. The Comintern was the weapon of choice. A few revolutions did break out, but they were quickly suppressed (the longest lasting one was in Hungary)—the Hungarian Soviet Republic—lasted only from 21 March 1919 to 1 August 1919. The Russian Bolsheviks were in no position to give any help. By 1921, Lenin, Trotsky, and Stalin realized that capitalism had stabilized itself in Europe and there would not be any widespread revolutions anytime soon. It became the duty of the Russian Bolsheviks to protect what they had in Russia, and avoid military confrontations that might destroy their bridgehead. Russia was now a pariah state, along with Germany. The two came to terms in 1922 with the Treaty of Rapallo that settled long-standing grievances. At the same time, the two countries secretly set up training programs for the illegal German army and air force operations at hidden camps in the USSR. Moscow eventually stopped threatening other states, and instead worked to open peaceful relationships in terms of trade, and diplomatic recognition.
Sources: en.wikipedia.org
Based on crystallography data of homologous NADP-dependent malic enzymes of mammalian origin, a 3D model for C4 pathway NADP-ME in plants has been developed, identifying the key residues involved in substrate-binding or catalysis. Dinucleotide binding involves two glycine-rich GXGXXG motifs, a hydrophobic groove involving at least six amino acid residues, and a negatively charged residue at the end of the βB-strand. The primary sequence of the first motif, 240GLGDLG245, is a consensus marker for phosphate binding, evidencing involvement with NADP binding, while the other glycine rich motif adopts a classical Rossmann fold—also a typical marker for NADP cofactor binding. Mutagenesis experiments in maize NADP-ME have supported the current model. Valine substitution for glycine in either motif region rendered the enzyme completely inactive while spectral analysis indicated no major changes from wild-type form. The data is suggestive of direct impairment at a key residue involved in binding or catalysis rather than an inter-domain residue influencing conformational stability. Additionally, a key arginine residue at site 237 has been shown to interact both with malate and NADP+ substrates, forming key favorable electrostatic interactions to the negatively charged carboxylic-acid and phosphate group respectively. Elucidation of whether the residue plays a role in substrate binding or substrate positioning for catalysis has yet to be determined.
=== Nucleic acid programmable protein array (NAPPA) === This system was first developed by LaBaer and colleagues in 2004 by using in vitro transcription and translation system. They use DNA template encoding the gene of interest fused with GST protein, and it was immobilized in the solid surface. Anti-GST antibody and biotinylated plasmid DNA were bounded in aminopropyltriethoxysilane (APTES)-coated slide. BSA can improve the binding efficiency of DNA. Biotinylated plasmid DNA was bound by avidin. New protein was synthesized by using cell-free expression system i.e. rabbit reticulocyte lysate (RRL), and then the new protein was captured through anti-GST antibody bounded on the slide. To test protein–protein interaction, the targeted protein cDNA and query protein cDNA were immobilized in a same coated slide. By using in vitro transcription and translation system, targeted and query protein was synthesized by the same extract. The targeted protein was bound to array by antibody coated in the slide and query protein was used to probe the array. The query protein was tagged with hemagglutinin (HA) epitope. Thus, the interaction between the two proteins was visualized with the antibody against HA.
== History == The origins of atmospheric pressure chemical ionization sources combined with mass spectrometry can be found in the 1960s in studies of ions in flames and of ion chemistry in corona discharges up to atmospheric pressure. The first application of APCI combined with mass spectrometry for trace chemical analysis was by the Franklin GNO Corporation who in 1971 developed an instrument combining APCI with ion mobility and mass spectrometry. Horning, Carroll and their co-workers in the 1970s at the Baylor College of Medicine (Houston, TX) demonstrated the advantages of APCI for coupling gas chromatography (GC) and liquid chromatography (LC) to a mass spectrometer. High sensitivity and simple mass spectra were shown in these studies. For LC-MS, the LC eluate was vaporized and ionized in a heated metal block. Initially, a 63Ni foil was used as a source of electrons to perform ionization. In 1975, a corona discharge electrode was developed, providing a larger dynamic response range. APCI with the corona discharge electrode became the model for modern commercially available APCI interfaces. In the late 1970s an APCI mass spectrometer system (the TAGA, for Trace Atmospheric Gas Analyzer), mounted in a van for mobile operation, was introduced by SCIEX, providing high sensitivity for monitoring polar organics in ambient air in real time. In 1981 a triple quadrupole mass spectrometer version was produced, allowing real-time direct air monitoring by APCI-MS/MS.
Sources: en.wikipedia.org
两者都是 GHS-R1a 激动剂，但 ipamorelin 在研究中显示出更高的生长激素释放选择性。早期资料显示它对皮质醇、催乳素与食欲的刺激弱于 GHRP-6。这些差异是相对程度，而非绝对区分。
公开资料中它主要以研究用肽的形式出现，未获主要监管机构批准用于治疗。可得材料通常标注仅供研究使用。任何临床用途的宣称都缺少监管依据。
序列中的 Aib 与 D-2-Nal 等非天然残基可提高对肽酶的抵抗能力，并影响受体结合的构象。这类修饰在合成肽设计中较为常见。它们也使常规氨基酸分析需要额外步骤才能确认序列。
Aib 即 α-氨基异丁酸，是一种非蛋白质源氨基酸，其侧链为两个甲基。它在肽链中倾向于诱导螺旋构象并限制骨架的柔性。这种刚性被认为有助于抵抗蛋白酶切割。