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内啡肽(Endorphin)的定义

内啡肽是由身体产生的小神经肽，用于减轻疼痛，因此被称为内啡肽（内源性吗啡的缩写）。术语“脑啡肽”（字面意思是“在头部”）也适用于内啡肽，但通常是指具有止痛特性的较小分子【1】。

Endorphins are small neuropeptides that are produced by the body and act to reduce pain hence, the name endorphin (a shortened version of endogenous morphine). The term "enkephalin" (meaning literally "in the head") is also applied to endorphins, but usually refers to smaller molecules that have pain-relieving properties【1】.

内啡肽(Endorphin)的3种相关多肽

Enkephalins: Met- and Leu-
Endorphins
Dynorphins

内啡肽是长度为2至39个氨基酸的神经肽。神经肽是在神经系统中产生和释放的肽分子，其作用类似于递质【2】。有三种不同的神经肽序列，包括脑啡肽、内啡肽和强啡肽【3】

Endorphins are neuropeptides that can range from 2 to 39 amino acids in length. Neuropeptides are peptide molecules produced and released in the nervous system that act like transmitters 【2】 There are three different neuropeptide sequences including enkephalins, endorphins, and dynorphins【3】

内啡肽(Endorphin)的发现

1975年，阿伯丁大学的John Hughes和Hans W.Kosterlitz分离出大脑中两种与阿片受体紧密结合的天然肽，并将其命名为脑啡肽。随后从垂体中分离出内啡肽分子【4】。

In 1975, John Hughes and Hans W. Kosterlitz of the University of Aberdeen isolated two naturally occurring peptides in the brain that bound tightly to the opiate receptors and named them enkephalins. The endorphin molecule was subsequently isolated from the pituitary gland 【4】.

内啡肽(Endorphin)的结构特征

迄今为止，已鉴定出四种不同的内啡肽。它们分别被称为：α-内啡肽，一种由16个残基组成的多肽；β-内啡肽，一种由31个残基组成的多肽；γ-内啡肽，一种由17个残基组成的多肽；以及S-内啡肽，一种由27个残基组成的多肽。与所有已知的多肽激素一样，这些不同类型的内啡肽以“前体”形式合成，即一种巨大的多肽，带有信号序列和在多肽翻译后成熟过程中被切割掉的额外序列。这方面最有趣的例子是垂体多激素前体，即促阿片黑素皮质素原，它包含β-促脂素、促黑素细胞激素（MSH）、内啡肽、脑啡肽和促肾上腺皮质激素（ACTH）的序列。合成后，这种肽在垂体中被切割生成ACTH和β-促脂素，而在中枢神经系统的加工过程中则产生内啡肽和脑啡肽，以及其他一些产物【5】。

Four distinct groups of endorphins have been identified to date. They have been termed: a-endorphin, a polypeptide with 16 residues; ß-endorphin, a polypeptide with 31 residues; ?-endorphin, a polypeptide with 17 residues; and S-endorphin, a polypeptide with 27 residues. These different types of endorphins, like all known polypeptide hormones, are synthesized in a "prepro" form that is one gigantic polypeptide with a signal sequence and additional sequences that are cleaved out during posttranslational maturation of the polypeptide. The most interesting example of this is the pituitary multihormone precursor termed pro-opiomelanocortin that contains the sequences for ß-lipotropin, melanocyte-stimulating hormone (MSH), endorphins, enkephalins, and adrenocorticotropic hormone (ACTH). After synthesis, this peptide is cleaved in the pituitary to generate ACTH and ß-lipotropin, while processing in the central nervous system produces endorphins and enkephalins, along with some other products 【5】.

内啡肽(Endorphin)的作用方式

受体使内啡肽能够发挥其特定功能。阿片受体是嵌入接收神经元细胞膜半流体基质中的大分子蛋白质。受体蛋白的表面包含一个区域，其大小和形状与内啡肽分子的结构精确匹配。内啡肽分子恰好嵌入特定的受体位点。神经肽与其特定受体（阿片受体）的结合会改变受体蛋白的三维结构，从而使神经元兴奋或抑制【6】。与内啡肽的情况一样，神经元的抑制会减少P物质的释放。换言之，阿片受体将内啡肽分子结构所编码的精确信息转化为特定的生理反应。因此，受体作为一种控制机制，从而调节内啡肽的功能【7】。

Receptors enable endorphins to perform their specific function. Opioid receptors are large protein molecules embedded in the semi-fluid matrix of the cell membrane of the receiving neuron. The surface of the receptor protein contains a region that is the precise size and shape to match the structure of the endorphin molecule. The endorphin molecule precisely fits into the specific receptor site. The binding of the neuropeptide with its specific receptor (opioid receptor) alters the three-dimensional shape of the receptor protein, thereby causing a neuron to be excited or inhibited【6】. As in the case of endorphins, inhibition of the neuron will reduce the release of substance P. In other words, the opioid receptor translates the precise messages encoded by the molecular structure of the endorphin molecule into a specific physiological response. Thus, receptors act as a control mechanism thereby regulating the function of endorphins【7】.

内啡肽(Endorphin)的功能

内啡肽并不被视为神经递质分子，而是被归类为神经调质，即它们通过多种与疼痛或愉悦相关的作用来调节神经递质的作用。内啡肽具有多种与缓解疼痛相关的神经学效应。外源性内啡肽（体外制备的内啡肽）的给药会刺激许多其他激素的释放，包括催乳素、促肾上腺皮质激素释放激素（ACTH）和抗利尿激素。吗啡的镇痛作用通常被认为是由其与内啡肽受体位点的结合引起的，但关于外源性内啡肽治疗的益处报道甚少。早期关于内啡肽功能的推测认为，它们是人体产生的天然止痛剂，用于在需要个体在受伤或压力下继续发挥功能的情况下缓解疼痛。这种情况的例子可能包括分娩、运动和战斗。几种治疗慢性疼痛的方法（针灸、直接电刺激大脑甚至催眠）可能通过诱导大脑和脊髓中脑啡肽或内啡肽的释放来发挥作用。这一假设基于以下发现：这些方法治疗疼痛的有效性可通过给予纳洛酮来阻断，纳洛酮是一种特异性阻断吗啡与阿片受体1结合的药物。

Endorphins are not considered to be neurotransmitter molecules, but are instead classified as neuromodulatory, that is, they modify the action of neurotransmitters through a number of effects associated with pain or pleasure. Endorphins exhibit a number of neurological effects associated with the relief of pain. The administration of exogenous endorphins (those prepared outside the body) stimulates the release of many other hormones including prolactin, ACTH, and antidiuretic hormone. The analgesic effects of morphine are commonly believed to be caused by binding to receptor sites for endorphins, but few beneficial effects of treatment with exogenous endorphins have been reported. Early speculations concerning the function of endorphins suggested that they were natural painkillers that the body produced to alleviate pain in circumstances requiring an individual to continue functioning in spite of injury or stress. Examples of such situations might include childbirth, exercise, and combat. Several procedures that treat chronic pain (acupuncture, direct electrical stimulation of the brain and even hypnosis) may act by inducing the release of enkephalins or endorphins in the brain and spinal cord. This hypothesis is based on the finding that the effectiveness of treating pain implemented by these procedures is blocked by administration of naloxone, a drug that specifically blocks the binding of morphine to the opiate receptor 【1】.

内啡肽(Endorphin)的相关文献

Book: Textbook of Biochemistry: With Clinical Correlations by Devlin TM.
Book: Animal Physiology by Eckert R.
Book: Neurobiology by Shepherd GM.
Book: The Brain by Iverson L.
Book: Molecular Expressions: Exploring the World of Optics and Microscopy Michael WD.
Book: Neural and Integrative Animal Physiology by Prosser CL.
Book:. Neuroscience by Barker RA

多肽H2N-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-COOH的合成步骤：

1、合成CTC树脂：称取1.1g CTC Resin（如初始取代度约为0.37mmol/g）和0.49mmol Fmoc-Tyr(tBu)-OH于反应器中，加入适量DCM溶解氨基酸（需要注意，此时CTC树脂体积会增大好几倍，避免DCM溶液过少），再加入1.22mmol DIPEA（Mw：129.1,d：0.740g/ml），反应2-3小时后，可不抽滤溶液，直接加入1ml的HPLC级甲醇，封端半小时。依次用DMF洗涤2次，甲醇洗涤1次，DCM洗涤一次，甲醇洗涤一次，DCM洗涤一次，DMF洗涤2次（这里使用甲醇和DCM交替洗涤，是为了更好地去除其他溶质，有利于后续反应）。得到  Fmoc-Tyr(tBu)-CTC Resin。结构图如下：

2、脱Fmoc：加3倍树脂体积的20%Pip/DMF溶液，鼓氮气30分钟，然后2倍树脂体积的DMF 洗涤5次。得到 H2N-Tyr(tBu)-CTC Resin 。（此步骤脱除Fmoc基团，茚三酮检测为蓝色，Pip为哌啶）。结构图如下：

3、缩合：取1.22mmol Fmoc-Ala-OH 氨基酸，加入到上述树脂里，加适当DMF溶解氨基酸，再依次加入2.44mmol DIPEA，1.16mmol HBTU。反应30分钟后，取小样洗涤，茚三酮检测为无色。用2倍树脂体积的DMF 洗涤3次树脂。（洗涤树脂，去掉残留溶剂，为下一步反应做准备）。得到Fmoc-Ala-Tyr(tBu)-CTC Resin。氨基酸：DIPEA：HBTU：树脂=3：6：2.85：1（摩尔比）。结构图如下：

4、依次循环步骤二、步骤三，依次得到

H2N-Ala-Tyr(tBu)-CTC Resin

Fmoc-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Gly-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Gly-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Gly-Gly-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

H2N-Gly-Gly-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

Fmoc-Tyr(tBu)-Gly-Gly-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin

以上中间结构，均可在专肽生物多肽计算器-多肽结构计算器中，一键画出。

最后再经过步骤二得到 H2N-Tyr(tBu)-Gly-Gly-Phe-Met-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Lys(Boc)-Ser(tBu)-Gln(Trt)-Thr(tBu)-Pro-Leu-Val-Thr(tBu)-Leu-Phe-Lys(Boc)-Asn(Trt)-Ala-Ile-Ile-Lys(Boc)-Asn(Trt)-Ala-Tyr(tBu)-CTC Resin，结构如下：

5、切割：6倍树脂体积的切割液（或每1g树脂加8ml左右的切割液），摇床摇晃 2小时，过滤掉树脂，用冰无水乙醚沉淀滤液，并用冰无水乙醚洗涤沉淀物3次，最后将沉淀物放真空干燥釜中，常温干燥24小试，得到粗品H2N-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-COOH。结构图见产品结构图。

切割液选择：1）TFA：H2O=95%：5%

2）TFA：H2O：TIS=95%：2.5%：2.5%

3）三氟乙酸：茴香硫醚：1，2-乙二硫醇：苯酚：水=87.5%：5%：2.5%：2.5%：2.5%

（前两种适合没有容易氧化的氨基酸，例如Trp、Cys、Met。第三种适合几乎所有的序列。）

6、纯化冻干：使用液相色谱纯化，收集目标峰液体，进行冻干，获得蓬松的粉末状固体多肽。不过这时要取小样复测下纯度 是否目标纯度。

7、最后总结：

杭州专肽生物技术有限公司（ALLPEPTIDE https://www.allpeptide.com）主营定制多肽合成业务，提供各类长肽，短肽，环肽，提供各类修饰肽，如：荧光标记修饰（CY3、CY5、CY5.5、CY7、FAM、FITC、Rhodamine B、TAMRA等），功能基团修饰肽（叠氮、炔基、DBCO、DOTA、NOTA等），同位素标记肽（N15、C13），订书肽（Stapled Peptide）,脂肪酸修饰肽（Pal、Myr、Ste），磷酸化修饰肽（P-Ser、P-Thr、P-Tyr），环肽（酰胺键环肽、一对或者多对二硫键环），生物素标记肽，PEG修饰肽，甲基化修饰肽等。

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