甘氨酰甘氨酰-L-苯丙氨酸 | 6234-26-0

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 天然氨基酸及其衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 甘氨酰甘氨酰-L-苯丙氨酸
• 英文名称: glycylglycyl-(L)-phenylalanine
• 英文别名: Gly-Gly-Phe；GGF；(2S)-2-[2-(2-aminoacetamido)acetamido]-3-phenylpropanoic acid；(S)-2-(2-(2-aminoacetamido)acetamido)-3-phenylpropanoic acid；H-Gly-Gly-Phe-OH；gly-Gly-L-Phe；(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoic acid
• CAS: 6234-26-0
• 化学式: C₁₃H₁₇N₃O₄
• mdl: MFCD00066054
• 分子量: 279.296
• InChiKey: KAJAOGBVWCYGHZ-JTQLQIEISA-N

物化性质

• 熔点：
  228-230 °C (decomp)
• 沸点：
  647.1±55.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -15°C

反应信息

• 作为反应物：
  描述：

  甘氨酰甘氨酰-L-苯丙氨酸 在 N-甲基吗啉 、 sodium hydroxide 、 三甲胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 6.25h， 生成 Boc-Gly-Gly-Phe-Met-OH
  参考文献：
  名称：

  Synthesis and biological evaluation of a metazocine-containing enkephalinamide. Evidence for nonidentical roles of the tyramine moiety in opiates and opioid peptides

  摘要：

  In an effort to test the hypothesis that the tyramine moiety present in opiates and in opioid peptides plays an identical functional role at opioid receptors, a hybrid enkephalinamide (3) that contains (-)-metazocine (4a) in place of Tyr was synthesized. It was found that 3 and its congeners are inactive or feebly active in the electrically stimulated guinea pig ileum and mouse vas deferens preparations. The results of these studies suggest that the tyramine moiety in opiates and related structures does not play the same functional role as that in the opioid peptides. It is suggested that the different functional roles of the tyramine moiety in opiates and opioid peptides is a consequence of different modes of interaction with common receptors.

  DOI：

  10.1021/jm00354a006
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 甲醇 、 palladium on activated charcoal 、 溶剂黄146 作用下， 生成 甘氨酰甘氨酰-L-苯丙氨酸
  参考文献：
  名称：

  THE USE OF HYDROGEN BROMIDE IN ACETIC ACID FOR THE REMOVAL OF CARBOBENZOXY GROUPS AND BENZYL ESTERS OF PEPTIDE DERIVATIVES¹

  摘要：

  DOI：

  10.1021/jo01366a011
• 作为试剂：
  描述：

  β-烟酰胺腺嘌呤二核苷酸 在 [Ir(III)(η5-pentamethylcyclopentadienyl)(H2O)3](SO4) 、 甘氨酰甘氨酰-L-苯丙氨酸 、 sodium formate 作用下， 以 aq. phosphate buffer 、 水 为溶剂， 生成 1,2-二氢烟酰胺腺嘌呤二核苷酸 、 1,6-二氢烟酰胺腺嘌呤二核苷酸 、 还原型辅酶Ⅰ
  参考文献：
  名称：

  用于转移氢化的可遗传编码的配体

  摘要：

  这里显示简单的三肽是铱催化转移氢化的通用配体，可提供大的加速效果。例如，具有 Gly-Gly-Phe 的水溶性铱络合物通过甲酸盐催化还原各种酮、醛和亚胺，其转换频率可与已建立的配体系统相媲美或优于这些。辅酶 NAD+ 到 NADH 的区域选择性还原说明了该系统在生物技术应用中的潜在效用。因为肽是可遗传编码的，它们代表了一类有吸引力的折叠配体，用于创建人工金属酶。

  DOI：

  10.1002/ejoc.201300340

文献信息

• Synthesis, properties, and reactions of α- and β-D-glucopyranosyl esters of some tripeptides
  作者：Štefica Valenteković、Dina Keglević

  DOI：10.1016/s0008-6215(00)85517-2

  日期：1980.6

  chromatography into the pure isomeric forms. Catalytic hydrogenolysis of the beta anomers, in the presence and absence of a strong acid, yielded the free 1-esters 2 beta, 9 beta, and 14 beta, which were characterised as the monoxalate or trifluoroacetate salts and as free bases. Similarly, the alpha anomers afforded 2 alpha, 9 alpha, and 14 alpha, whereas omission of the strong acid led to accompanying 1

  由2,3,4,6-四-O-苄基合成2,3,4,6-四-O-苄基-1-O-（N-苄氧基羰基三肽基）-D-吡喃葡萄糖），8和13。 -α-D-吡喃葡萄糖和在咪唑存在下合适的N-保护的三肽（Gly-Cly-Gly-，L-Phe-Gly-Gly-和Gly-Gly-L-Phe-）的活性酯；分离异头物混合物并表征α和β异头物。含有Gly-Gly-Phe-的L和D对映异构体（比例约为3：1）作为糖苷配基的13的β异构体可以通过柱色谱法分离为纯的异构体形式。在存在和不存在强酸的情况下，β端基异构体的催化氢解反应会生成游离的1酯2 beta，9 beta和14 beta，它们被表征为一x酸酯或三氟乙酸盐和游离碱。同样，α异头物提供2个α，9 alpha和14 alpha，而忽略强酸会导致伴随的1导致2的酰基迁移，从而生成2-O-酰基衍生物。将所有制备的化合物转化为N-乙酰基和/或过乙酰化衍生物。带电和不带电形式的1酯2
• [EN] PEPTIDE-CONJUGATED PRODRUGS<br/>[FR] PROMÉDICAMENTS CONJUGUÉS À UN PEPTIDE
  申请人：UNIV BRANDEIS

  公开号：WO2021055690A1

  公开（公告）日：2021-03-25

  The present disclosure relates to a conjugated prodrug comprising a peptide conjugated to an antibiotic molecules via a cleavable linker and pharmaceutical compositions thereof. Also disclosed are methods of enhancing the intracellular concentration of an antibiotic agent in a bacterium and methods of treating a patient for a bacterial infection.

  本公开涉及一种共轭前药，包括通过可切割连接物将肽与抗生素分子结合在一起的药物，并其制药组合物。还公开了增强细菌内抗生素药物浓度的方法以及治疗患有细菌感染的患者的方法。
• [EN] NEODEGRADER CONJUGATES<br/>[FR] CONJUGUÉS DE TYPE NEODEGRADER
  申请人：ORUM THERAPEUTICS INC

  公开号：WO2021198965A1

  公开（公告）日：2021-10-07

  The present disclosure provides neoDegraders and neoDegraders conjugated to binding moieties. Also provided are compositions comprising the conjugates. The compounds and compositions are useful for treating a disease or condition, e.g., cancer, in a subject in need thereof.

  本公开提供了与结合基团结合的neoDegraders和neoDegraders。还提供了包含这些结合物的组合物。这些化合物和组合物对于治疗患有疾病或症状的受试者（例如癌症）是有用的。
• Inhibitors of Tripeptidyl Peptidase II. 2. Generation of the First Novel Lead Inhibitor of Cholecystokinin-8-Inactivating Peptidase:  A Strategy for the Design of Peptidase Inhibitors
  作者：C. Robin Ganellin、Paul B. Bishop、Ramesh B. Bambal、Suzanne M. T. Chan、James K. Law、Benoit Marabout、Pratibha Mehta Luthra、Andrew N. J. Moore、Olivier Peschard、Pierre Bourgeat、Christiane Rose、Froylan Vargas、Jean-Charles Schwartz

  DOI：10.1021/jm990226g

  日期：2000.2.1

  fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 microM) and Ala-Pro-Ala-OH (K(i) = 3 microM) and dipeptide

  失活胆囊收缩素8（CCK-8）的肽酶是一种丝氨酸肽酶，已证明是三肽基肽酶II的膜结合同工型（EC 3.4.14.10）。它在Met-Gly键处裂解神经递质CCK-8硫酸盐，得到Asp-Tyr（SO（3）H）-Met-OH + Gly-Trp-Met-Asp-Phe-NH（2）。为了寻找该肽酶的可逆抑制剂，使用基于人工底物Ala-Ala-Phe-酰胺基甲基香豆素水解的荧光分析法来表征酶促结合亚位点。对具有各种烷基或芳基侧链的一系列二肽和三肽进行了研究，以确定可结合的体积并探讨疏水相互作用的可能性。根据这项初步研究，三肽Ile-Pro-Ile-OH（K（i）= 1 microM）和Ala-Pro-Ala-OH（K（i）= 3 microM）和二肽酰胺Val-Nvl-NHBu（K（ i）= 3 microM）作为线索出现。这些结构的比较导致Val-Pro-NHBu（K（i）= 0.57 micr
• Linear energy correlations and failures in the low-energy tandem mass spectra of protonatedN-benzoylated tripeptides: Tools for probing mechanisms of CAD processes
  作者：Daniel G. Morgan、Maurice M. Bursey

  DOI：10.1002/jms.1190300410

  日期：1995.4

  The backbone cleavages for three series of protonated N-benzoyl tripeptide ions were studied in a hybrid tandem mass spectrometer: (i) benzoyl-Gly-Gly-Xxx, where Xxx = Gly, Ala, Val, Leu, Ile, Phe, Tyr, Met, Glu, Pro and Trp, (ii) benzoyl-Gly-Xxx-Gly, where Xxx = Gly, Ala, Leu, Phe, Tyr, Met and Trp, and (iii) benzoyl-Xxx-Gly-Gly, where Xxx = Gly, Ala, Val, Leu, Ile, Phe, Tyr, Met, Pro and Trp. C-Terminal y-type ions and N-terminal a- and b-type ions were noted in all three cases. For benzoyl-Gly-Gly-Xxx, a linear relationship between log (y1/b2) and the proton affinity of the C-terminal amino acid substituents was found: as the proton affinity of the C-terminal residue increases, the fraction of y1 ion formation increases. A similar relationship was noted for the benzoyl-Xxx-Gly-Gly tripeptides between log (y2/b1) and the proton affinity of the N-terminal amino acid substituent: as the proton affinity of the N-terminal residue increases, the fraction of b1 ion formation increases. For the series benzoyl-Gly-Xxx-Gly, these relationships did not hold true. These observations point to similar reaction pathways throughout the benzoyl-Gly-Gly-Xxx series and also similar pathways throughout the benzoyl-Xxx-Gly-Gly, but pathways that are substituent dependent for benzoyl-Gly-Xxx-Gly. The increased correlation coefficients for benzoyl-Gly-Gly-Xxx and benzoyl-Xxx-Gly-Gly when compared with the free tripeptides, suggest that fewer interfering competitive reactions exist, as fewer possibilities for internal hydrogen bonding exist in the N-benzoyl derivatives versus the free compounds.

  在一台混合串联质谱仪上，研究了三种系列的质子化N-苯甲酰三肽离子的骨架断裂：（i）苯甲酰-Gly-Gly-Xxx，其中Xxx = Gly、Ala、Val、Leu、Ile、Phe、Tyr、Met、Glu、Pro和Trp，（ii）苯甲酰-Gly-Xxx-Gly，其中Xxx = Gly、Ala、Leu、Phe、Tyr、Met和Trp，以及（iii）苯甲酰-Xxx-Gly-Gly，其中Xxx = Gly、Ala、Val、Leu、Ile、Phe、Tyr、Met、Pro和Trp。在所有三种情况下，都观察到了C端y型离子和N端a型及b型离子。对于苯甲酰-Gly-Gly-Xxx，发现log（y1/b2）与C端氨基酸取代基的质子亲和力之间存在线性关系：随着C端残基的质子亲和力增加，y1离子的形成分数增加。对于苯甲酰-Xxx-Gly-Gly三肽，log（y2/b1）与N端氨基酸取代基的质子亲和力之间存在类似的关系：随着N端残基的质子亲和力增加，b1离子的形成分数增加。对于苯甲酰-Gly-Xxx-Gly系列，这些关系并不成立。这些观察结果表明，在苯甲酰-Gly-Gly-Xxx系列和苯甲酰-Xxx-Gly-Gly系列中存在类似的反应途径，但对于苯甲酰-Gly-Xxx-Gly，途径依赖于取代基。与自由三肽相比，苯甲酰-Gly-Gly-Xxx和苯甲酰-Xxx-Gly-Gly的相关系数增加，表明存在的干扰竞争反应较少，因为在N-苯甲酰衍生物中内部氢键的可能性比自由化合物少。

表征谱图