This is a working overview of deamidation, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-09-13. Anything still debated is marked as such rather than presented as settled.
市售的胸腺素α1通常以冻干粉形式提供，溶解后用于注射。其氨基酸组成包括多个酸性残基，因此在中性pH下带负电荷。该肽可溶于水和生理盐水，但在有机溶剂中溶解度有限。储存条件通常为冻干状态下负20摄氏度，溶解后需冷藏并避免反复冻融。常见的同义词包括胸腺肽α1、thymalfasin和Tα1。
胸腺素α1（thymosin alpha 1，Tα1）是一种由28个氨基酸组成的酸性肽，N端被乙酰化，分子量约为3108道尔顿。该肽最早从牛胸腺组织提取物中分离，属于胸腺素组分5的一个成分。其序列在不同哺乳动物中高度保守，提示其具有基本的生物学功能。名称中的“α1”指其在电泳中的迁移位置，并非表示亚型编号。它既存在于胸腺，也存在于脾脏和淋巴结等免疫组织。
Identity and purity are normally assessed by reversed-phase high-performance liquid chromatography, which separates the peptide from related impurities and truncation products. Mass spectrometry confirms molecular mass and detects modifications such as deamidation or oxidation. Amino acid analysis and peptide mapping provide additional sequence-level confirmation. For research material, a certificate of analysis typically reports these results together with water content and counter-ion identity, since the lyophilized powder is often supplied as an acetate or trifluoroacetate salt.
Several factors accelerate degradation: alkaline pH, elevated temperature, exposure to oxidants, and the presence of residual moisture. Deamidation of asparagine residues and oxidation of methionine are the most commonly reported degradation routes. Because the peptide lacks disulfide bonds, it does not undergo the thiol-related aggregation seen in some other biologics, but physical aggregation can still occur at high concentration. Stability data are product-specific, and extrapolating shelf life between formulations is not reliable.
| Property | Value | Notes |
|---|---|---|
| 化学分类 | 线性肽 | 由28个氨基酸组成 |
| 分子量 | 约3108 Da | 合成版本一致 |
| 外观 | 白色至类白色粉末 | 冻干品 |
| 溶解度 | 易溶于水 | 微溶于有机溶剂 |
| 储存温度 | -20°C（冻干） | 溶解后2-8°C |
Overall evidence quality varies considerably. A large share of published reports come from single centers, rely on surrogate immunological markers, or lack adequate control groups. Systematic reviews have highlighted this heterogeneity as a barrier to pooling results. Open questions include which patients, if any, might benefit, what treatment duration is appropriate, and whether any effect is independent of standard care. The peptide is often described as an immune modulator rather than a therapy for one disease, which complicates confirmatory trial design.
Thymosin alpha 1 was identified in 1977 as a component of thymosin fraction 5, a heterogeneous preparation used in early studies of thymic function. Investigators purified the active material and determined its amino acid sequence, which enabled chemical synthesis. Work in the following decades concentrated on T-cell maturation and immune reconstitution in animals and small human cohorts. Early preparations varied in composition, so results from that period are difficult to compare with studies using defined synthetic peptide.
Identity and purity are assessed with a small set of standard peptide methods. Reversed-phase high-performance liquid chromatography separates the main peak from truncated or oxidized species, and its area percentage is the usual purity measure. Mass spectrometry confirms the observed molecular mass against the expected value, while amino acid analysis or peptide mapping checks composition and sequence. Specifications for research-grade material are often stated as 95 percent or higher, though the exact limit depends on the supplier and the intended use.
Laboratory supplies of the peptide usually arrive as a lyophilized powder in sealed vials. The powder is hygroscopic, so a vial should be allowed to reach room temperature before it is opened to prevent condensation on the contents. Weighing and transfer are best performed in a low-humidity environment with clean tools. Once dissolved, the solution should be mixed gently rather than vortexed, because foaming and shear can reduce recovery of the peptide.
The peptide is generated in cells by cleavage of prothymosin alpha, a larger acidic protein encoded by the PTMA gene. Prothymosin alpha is expressed in many tissues, not only in the thymus, and its functions include nuclear roles in chromatin-related processes. The 28-residue fragment corresponds to the N-terminal portion of that precursor. How the cleavage occurs and how the fragment's concentration is regulated remain open questions; circulating amounts are small and difficult to measure reliably with routine assays.
Thymosin alpha 1 is a short peptide first isolated from bovine thymus tissue in the early 1970s during fractionation work aimed at identifying factors that influence T cell development. It belongs to a family of acidic thymic peptides, and the original preparations contained several components that were later separated by chromatography. The compound is now produced synthetically rather than extracted from tissue, which removes batch variability tied to animal sourcing. Researchers describe it as an immunomodulatory peptide because laboratory studies show effects on several cell types of the innate and adaptive immune systems.
The molecule consists of 28 amino acid residues with an acetyl group attached to the N-terminal serine. Its sequence is acidic overall, with several glutamic and aspartic acid residues distributed along the chain and no cysteine, so disulfide bridges do not form. The peptide carries a net negative charge at physiological pH. Because the N-terminus is blocked, the intact molecule resists degradation by many aminopeptidases, which contributes to its stability in biological fluids.
临床研究将Tα1用于慢性病毒感染、肿瘤辅助治疗和疫苗佐剂等场景。部分试验报告了免疫学指标改善，但临床终点获益在不同研究中并不一致。系统综述指出，研究间在人群、剂量和联合方案上差异较大，难以汇总结论。因此，Tα1的确切临床地位仍属开放问题，需要更多高质量随机对照试验来澄清。其机制研究也需从体外实验向体内模型推进。
胸腺素α1对免疫系统的影响涉及多种细胞类型。研究表明，它可促进未成熟T细胞向成熟T细胞分化，并增强T细胞对抗原刺激的增殖反应。树突状细胞在Tα1存在下表达更高水平的共刺激分子，从而更有效地呈递抗原。此外，自然杀伤细胞的活性也观察到上升。这些效应并非直接杀伤病原体，而是调节宿主免疫应答的强度与方向。
在信号层面，Tα1可能通过Toll样受体等模式识别受体发挥作用。部分实验显示，它能激活髓样分化因子88依赖的通路，进而促进核因子κB进入细胞核。这导致白细胞介素2、干扰素γ和白细胞介素12等细胞因子的转录增加。这些细胞因子偏向辅助性T细胞1型应答，有助于细胞免疫。然而，具体受体和结合位点尚未完全确定，不同实验模型的结果存在差异。
Phosphoproteomics is a branch of proteomics that identifies, catalogs, and characterizes proteins containing a phosphate group as a posttranslational modification. Phosphorylation is a key reversible modification that regulates protein function, subcellular localization, complex formation, degradation of proteins and therefore cell signaling networks. With all of these modification results, it is estimated that between 30–65% of all proteins may be phosphorylated, some multiple times. Based on statistical estimates from many datasets, 230,000, 156,000 and 40,000 phosphorylation sites should exist in human, mouse, and yeast, respectively. Compared to expression analysis, phosphoproteomics provides two additional layers of information. First, it provides clues on what protein or pathway might be activated because a change in phosphorylation status almost always reflects a change in protein activity. Second, it indicates what proteins might be potential drug targets as exemplified by the kinase inhibitor Gleevec. While phosphoproteomics will greatly expand knowledge about the numbers and types of phosphoproteins, its greatest promise is the rapid analysis of entire phosphorylation based signalling networks.
=== Alcohols === Alcohols are commonly used as disinfectants and antiseptics. Alcohols kill vegetative bacteria, most viruses and fungi. Ethyl alcohol, n-propanol and isopropyl alcohol are the most commonly used antimicrobial agents. Methanol is also a disinfecting agent but is not generally used as it is highly poisonous. Escherichia coli, Salmonella, and Staphylococcus aureus are a few bacteria whose growth can be inhibited by alcohols. Alcohols have a high efficiency against enveloped viruses (60–70% ethyl alcohol) 70% isopropyl alcohol or ethanol are highly effective as an antimicrobial agent. In the presence of water, 70% alcohol causes coagulation of the proteins thus inhibiting microbial growth. Alcohols are not quite efficient when it comes to spores. The mode of action is by denaturing the proteins. Alcohols interfere with the hydrogen bonds present in the protein structure. Alcohols also dissolve the lipid membranes that are present in microorganisms. Disruption of the cell membrane is another property of alcohols that aids in cell death. Alcohols are cheap and effective antimicrobials. They are widely used in the pharmaceutical industry. Alcohols are commonly used in hand sanitizers, antiseptics, and disinfectants.
Apixaban During the SAR development of apixaban there were three groups that needed to be tested to attain maximum potency and bioavailability. The first group to be tested was the non-active site as it needs to be stabilized before SAR testing on the p-methoxyphenyl group (S1 binding moiety). There are several of groups that increase the potency of the compound, mostly amides, amines and tetrazoles but also methylsulfonyl and trifluoromethyl groups. Of these groups, carboxamide has the greatest binding and had similar clotting activity as the compounds. In dog testing, this compound with a carboxamide group called 13F, showed a great pharmacokinetical profile, a low clearance and adequate half-life and volume of distribution. Due to the success of finding a stabilizing group, SAR research for S1 binding moiety (p-methoxyphenyl) was discontinued. In the S4 binding group, N-methylacetyl and lactam analogues proved to have a very high binding affinity for FXa, showed great clotting and selectivity versus other proteases. Orientation turned out to be important as N-methyl acetyl, compared to acetamide, had a 300 fold lower binding ability to FXa due to unfavorable planarity close to the S4 region binding site.
== Mechanism == Riboflavin is converted into catalytically active cofactors FAD and FMN by the actions of riboflavin kinase EC 2.7.1.26, which converts it into FMN, and FAD synthetase EC 2.7.7.2, which adenylates FMN to FAD. The RFK module phosphorylates the riboflavin substrate and converts it into FMN, which is then released from the module. This reaction is dependent on an ATP molecule stabilized by an Mg2+ ion, which causes only a single phosphate group to leave the ATP and bond to riboflavin. The released FMN then joins to the N-terminal FMNAT module and is adenylated, with the adenylyl group of ATP attaching to the phosphate group on FMN and the diphosphate group leaving. ATP + riboflavin ⇌ ADP + FMN ATP + FMN ⇌ diphosphate + FAD
Sources: en.wikipedia.org
== Single-substrate reactions == Enzymes with single-substrate mechanisms include isomerases such as triosephosphateisomerase or bisphosphoglycerate mutase, intramolecular lyases such as adenylate cyclase, and the hammerhead ribozyme, an RNA lyase. However, some enzymes that only have a single substrate do not fall into this category of mechanisms. Catalase is an example of this, as the enzyme reacts with a first molecule of hydrogen peroxide substrate, becomes oxidised and is then reduced by a second molecule of substrate. Although a single substrate is involved, the existence of a modified enzyme intermediate means that the mechanism of catalase is actually a ping–pong mechanism, a type of mechanism that is discussed in the Multi-substrate reactions section below.
IUPAC recommends the names lanthanoids and actinoids to avoid ambiguity, as the -ide suffix typically denotes a negative ion; however lanthanides and actinides remain common. With the increasing recognition of lutetium and lawrencium as d-block elements, some authors began to define the lanthanides as La–Yb and the actinides as Ac–No, matching the f-block. The transactinides or superheavy elements are the short-lived elements beyond the actinides, starting at lawrencium or rutherfordium (depending on where the actinides are taken to end). Many more categorizations exist and are used according to certain disciplines. In astrophysics, a metal is defined as any element with atomic number greater than 2, i.e. anything except hydrogen and helium. The term "semimetal" has a different definition in physics than it does in chemistry: bismuth is a semimetal by physical definitions, but chemists generally consider it a metal. A few terms are widely used, but without any very formal definition, such as "heavy metal", which has been given such a wide range of definitions that it has been criticized as "effectively meaningless". The scope of terms varies significantly between authors. For example, according to IUPAC, the noble gases extend to include the whole group, including the very radioactive superheavy element oganesson. However, among those who specialize in the superheavy elements, this is not often done: in this case "noble gas" is typically taken to imply the unreactive behaviour of the lighter elements of the group.
Education in spiritual and religious matters is also required by the American Psychiatric Association, however, far less attention is paid to the damage that more rigid, fundamentalist faiths commonly practiced in the United States can cause. This theme has been widely politicized in 2018 such as with the creation of the Religious Liberty Task Force in July of that year. Also, many providers and practitioners in the United States are only beginning to realize that the institution of mental healthcare lacks knowledge and competence of many non-Western cultures, leaving providers in the United States ill-equipped to treat patients from different cultures.
The United States' Center for Drug Evaluation and Research officially recommends that drugs past their expiration date be disposed. It has been argued that this practice is wasteful, since consumers and medical facilities are encouraged to purchase fresh medication to replace their expired products, also resulting in additional profits for pharmaceutical firms.
=== General ethical issues === If the creation of human DNA through artificial gene synthesis were to become technically feasible, several ethical and social issues have been identified by researchers. Scholars such as Adrian Villalba and Anna Smajdor have noted that synthetic DNA may challenge existing assumptions about the nature and significance of human genetic material. One area of concern involves the concept of genetic ownership. If a person’s DNA sequence can be artificially recreated in the laboratory, it becomes unclear who holds rights or control over the resulting material, and whether current legal and ethical frameworks are adequate to address such cases. There are also questions about identity. Human genomes have traditionally been viewed as closely linked to personal identity and biological heritage. However, the possibility of reconstructing or redesigning genomic sequences through synthetic DNA would significantly weaken this association. If genomes can be created, modified, or replicated independently of natural inheritance, the view that genetic makeup rigidly determines personal traits becomes increasingly difficult to sustain. In this context, synthetic DNA is proposed as effectively undermining genetic determinism and prompting a re-evaluation of assumptions about the role of genes in shaping individual identity. Privacy is another significant issue. The possibility of synthesizing sequences identical or similar to those of existing individuals raises concerns about genetic data protection and potential misuse.
Sources: en.wikipedia.org
Propoxyphene should be used with extreme caution, if at all, in patients who have a history of substance/drug/alcohol abuse, depression with suicidal tendency, or who already take medications that cause drowsiness (e.g., antidepressants, muscle relaxants, pain relievers, sedatives, tranquilizers). Fatalities have occurred in such patients when propoxyphene was misused. Because of potential for side effects, this drug is on the list for high-risk medications in the elderly. On November 19, 2010, the FDA requested manufacturers withdraw propoxyphene from the US market, citing heart arrhythmia in patients who took the drug at typical doses. Tramadol, which lacks the cardiotoxicity, has been recommended instead of propoxyphene, as it is also indicated for mild to moderate pain, and is less likely to be misused or cause addiction than other opioids.
== Pharmacology == Mycophenolate can be derived from the fungi Penicillium stoloniferum, P. brevicompactum and P. echinulatum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It reversibly inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes. Other cells recover purines via a separate salvage pathway and are thus able to escape the effect. Mycophenolate is potent and can, in many contexts, be used in place of the older anti-proliferative azathioprine. It is usually used as part of a three-compound regimen of immunosuppressants, also including a calcineurin inhibitor (ciclosporin or tacrolimus) and a glucocorticoid (e.g. dexamethasone or prednisone).
Two registrational trials have evaluated vaccine candidates in active immunization strategies against S. aureus infection. In a phase II trial, a bivalent vaccine of capsular proteins 5 & 8 was tested in 1804 hemodialysis patients with a primary fistula or synthetic graft vascular access. After 40 weeks following vaccination a protective effect was seen against S. aureus bacteremia, but not at 54 weeks following vaccination. Based on these results, a second trial was conducted which failed to show efficacy. Merck tested V710, a vaccine targeting IsdB, in a blinded randomized trial in patients undergoing median sternotomy. The trial was terminated after a higher rate of multiorgan system failure–related deaths was found in the V710 recipients. Vaccine recipients who developed S. aureus infection were five times more likely to die than control recipients who developed S. aureus infection. Investigators have suggested that a multiple-antigen vaccine would be more effective, but a lack of biomarkers defining human protective immunity keep these proposals in the logical, but strictly hypothetical arena.
EPCs also have variable phenotypic markers used for identification. Unfortunately, there are no unique markers for endothelial progenitors that are not shared with other endothelial or hematopoietic cells, which has contributed to the historical controversy surrounding the field. A detailed overview of current markers can be found in the following table.
== Structure and function == GMP synthase forms a tetramer in an open box shape, which is a dimer of dimers. The R interfaces are held together with a hydrophobic core and a beta sheet, while the P dimer interfaces do not have a hydrophobic core and are more variable than the R interfaces. This enzyme also binds several ligands, including phosphate, pyrophosphate, AMP, citrate and Magnesium.
Sources: en.wikipedia.org
它不是经典的内分泌激素，而是一种免疫调节肽。其作用主要通过局部免疫细胞间的信号传递实现，而非经血液循环作用于远隔器官。
天然胸腺素α1主要从胸腺组织提取，也可在脾脏和淋巴结中检出。目前研究和临床使用的多为化学合成版本，不再依赖动物组织。
胸腺素组分5是牛胸腺提取物的粗组分，包含多种肽。胸腺素α1是其中一种被纯化和表征的单一肽，具有明确的28个氨基酸序列。
Dry lyophilized powder tolerates short ambient exposure during handling and shipping. Long-term room-temperature storage is not recommended because moisture uptake and slow degradation can occur over months. Storage at minus twenty degrees Celsius is the common practice for extended periods.