今天为大家带来一篇关于多肽和蛋白质之间解离机制探究的一篇文章，我将结合这篇文章中的一些具体参数简要谈一下各个自由能方法，虽然这篇文章比较久远，但是觉得比较有价值，因此整理之后发到了此公众号上：

司美格鲁肽又名索马鲁肽，英文名 Semaglutide，是一种胰高血糖素样肽-1 ( GLP-1) 类似物，序列如下图。分子式: C187H291N45059，作为一种长效 GLP-I 受体激动剂，每周只须注射1次，能用于辅助饮食控制和运动以改善2型糖尿病患者的血糖控制，同时能够降低患者体重。

抗体偶联药物 (ADC)，强效小分子细胞毒素通过化学键与单克隆抗体结合，比抗体具有更复杂的结构。本文详细描述了应用物理化学方法对抗体偶联药物进行表征研究。对于特定 ADC 最合适的方法，取决于接头、药物和药物的性质，偶联位点的选择（赖氨酸、链间半胱氨酸、Fc聚糖）以及分析技术的改进。例如蛋白质质谱和毛细管电泳技术可以显著提高研究水平，可用于产品表征、常规批次放行和稳定性研究。

日本研究人员首次制造了全氟铜苯（C8F8）。该分子做为一个盒状结构可以捕获并保留单个电子，这是量子力学“盒子中的粒子”原理的一项罕见的研究发现。

现如今多肽合成的办法首要有两种：即 Fmoc 和 t Boc 。因为 Fmoc 比 tBoc 具有更多的优势，所以让大家比较认可的是 Fmoc 法。而多肽合成是一个重复添加氨基酸的进程，合成方向是从 C 端（羧基端）向 N 端（氨基端）进行；从前多肽合成大多是在液相中进行，而如今大多选用固相合成，然后大大的降低了每步商品提纯的难度；为了防止副反响的发作，合成柱和添加的氨基酸的侧链都是预先被维护的，只要羧基端是游离的，并且在反响之前有必要先用化学试剂活化它。

The passage discusses the stability challenges of peptide drugs and various strategies to enhance their stability. Peptide drugs are prone to degradation through mechanisms such as oxidation, hydrolysis, and incorrect disulfide bond formation, which shorten their half-life and require frequent dosing. To address these issues, approaches such as site-directed mutagenesis, chemical modification (e.g., PEGylation), and gene fusion with larger proteins like albumin or antibody fragments are explored to increase their molecular stability and extend half-life. Additionally, the use of additives, lyophilization, and surfactants can improve peptide stability during storage and administration. These strategies aim to reduce degradation, enhance bioavailability, and improve therapeutic efficacy.

The passage discusses the different physical forms of peptides, such as powder or crystalline solids, and provides detailed guidance on how to properly store them. For long-term storage, peptides should be kept in a dark environment at -20°C or lower, while short-term storage can be done at 4°C. Transport at room temperature is generally safe for short periods. Peptides in solution should ideally be stored in a slightly acidic buffer at -20°C. Peptides containing Cys, Trp, Met, Asn, or Gln require extra care due to their susceptibility to oxidation and degradation. Additionally, all storage containers should be sealed to prevent moisture or air exposure, and sunlight or high temperatures should be avoided.

Solid-phase peptide synthesis is a major breakthrough in peptide synthesis chemistry. Its most significant feature is that there is no need to purify intermediate products, allowing the synthesis process to proceed continuously, thus laying the foundation for the automation of peptide synthesis. Currently, fully automated peptide synthesis is primarily based on solid-phase synthesis. The basic process is as follows: Based on Fmoc chemistry, the carboxyl group of the C-terminal amino acid of the target peptide to be synthesized is first covalently bonded to an insoluble polymer resin. The amino group of this amino acid is used as the starting point for peptide synthesis. A peptide bond is then formed by reacting the activated carboxyl group of the next amino acid with the amino group of the growing peptide chain. By continuously repeating this process, a peptide is obtained. Depending on the amino acid composition of the peptide, the post-treatment methods and purification techniques can vary.

The rapid development of biotechnology has significantly advanced the research and production of peptide and protein-based drugs. Over 40 key therapeutic drugs are on the market, and more than 700 biotech drugs are in various stages of clinical trials, with over 200 in the final approval stages.

1. Classification by Secretion Sites:
   - Vasopressin and Derivatives: Includes vasopressin, tannate vasopressin, and derivatives such as desmopressin.
   - Oxytocin and Derivatives: Includes oxytocin, desamino oxytocin, and oxytocin tartrate.
   - Corticotropin and Derivatives: Includes ACTH and modified versions like ACTH-Zn.
   - Hypothalamic-Pituitary Peptide Hormones: Includes gonadotropin-releasing hormone and growth hormone-releasing hormone.
   - Digestive Hormones: Gastrin, secretin, and cholecystokinin peptides.
   - Other Peptides: Includes thymosin α1, glucagon, and endorphins.

2. Classification by Function:
   - Peptide Vaccines: Used for infectious diseases like hepatitis, malaria, and HIV. Synthetic peptide vaccines are promising as they avoid the risks associated with live or inactivated vaccines.
   - Antitumor Peptides: Peptides that inhibit tumor growth, such as those that target specific regulatory factors involved in cancer progression.
   - Antiviral Peptides: Peptides that interfere with virus replication or binding to host cells, such as defensins and melittin.
   - Peptide-Directed Drugs: Target specific cells, like tumor cells, by linking toxic substances to peptides, reducing side effects.
   - Cytokine Mimetic Peptides: Small peptides mimicking cytokines (e.g., human erythropoietin) are being researched for their potential to stimulate immune responses or cell growth.
   - Thymopentin: A synthetic peptide that regulates immune function and is widely used as an immunomodulator.
   - Interferons: Proteins with antiviral and antitumor properties, produced through recombinant technology.
   - Antibacterial Peptides: Short peptides with antibacterial properties, resistant to traditional antibiotic resistance mechanisms, are being developed as new treatments for infections and cancer.

Peptides with a molecular weight below 1kDa possess ten major physiological functions.

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