Fmoc-Thr(^tBu)-HMPP | 864876-97-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Thr(^tBu)-HMPP
• 英文别名: Fmoc-L-Thr(tBu)-MPPA；3-[4-[[(2S,3R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]butanoyl]oxymethyl]phenoxy]propanoic acid
• CAS: 864876-97-1
• 化学式: C₃₃H₃₇NO₈
• 分子量: 575.659
• InChiKey: IRDBQOISHSANNE-DFXYEROKSA-N

物化性质

• 沸点：
  742.8±60.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.69
• 重原子数：
  42.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  120.39
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Fmoc-L-缬氨酸 、 Fmoc-Thr(^tBu)-HMPP 、 FMOC-O-叔丁基-L-丝氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 在 6-氯-1-羟基苯并三氮唑 、 N,N'-二异丙基碳二亚胺 、 哌嗪 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以24 mg的产率得到preptin-(1-4)
  参考文献：
  名称：

  Synthesis of truncated analogues of preptin-(1–16), and investigation of their ability to stimulate osteoblast proliferation

  摘要：

  Preptin, a 34-amino acid residue peptide hormone is co-secreted with insulin from the β-pancreatic cells and is active in fuel metabolism. We have previously established that a shorter fragment of preptin, namely preptin-(1–16), stimulates bone growth by proliferation and increasing the survival rate of osteoblasts. This was demonstrated in both in vitro and in vivo models. These findings suggest that preptin-(1–16) could play an important role in the anabolic therapy of osteoporosis. However, due to the large size of the peptide it is not an ideal therapeutic agent. The aim of this study was to identify the shortest preptin analogue that retains or even increases the bone anabolic activity as compared to the parent preptin-(1–16) peptide. Truncations were made in a methodical manner from both the N-terminus and the C-terminus of the peptide, and the effect of these deletions on the resulting biological activity was assessed. In order to improve the enzymatic stability of the shortest yet active analogue identified, ruthenium-catalysed ring closing metathesis was used to generate a macrocyclic peptide using allylglycine residues as handles for ring formation. We have successfully identified a short 8-amino acid preptin (1–8) fragment that retains an anabolic effect on the proliferation of primary rat osteoblasts and enhances bone nodule formation. Preptin (1–8) is a useful lead compound for the development of orally active therapeutics for the treatment of osteoporosis.

  DOI：

  10.1016/j.bmc.2014.05.026

文献信息

• [EN] TUMOUR-TARGETING PEPTIDE VARIANTS<br/>[FR] VARIANTS PEPTIDIQUES CIBLANT DES TUMEURS
  申请人：CANCER RESEARCH TECH LTD

  公开号：WO2018197490A1

  公开（公告）日：2018-11-01

  The present invention provides a peptide that selectively binds ανβ6 integrin, the peptide having an amino acid sequence comprising the motif X1BnRGDLX2X3X4 ZmX5, wherein X1 is any D-amino acid, Bn is a sequence of any n amino acids, which may be natural or unnatural, D- or L-, and may be the same or different, wherein n is a number between 1 and 10, X2 and X3 are independently selected from any amino acid, X4 is Leu or Ile, Zm is a sequence of any m amino acids, which may be natural or unnatural, D- or L-, and may be the same or different, wherein m is a number between 1 and 10, X5 is any L- or D-amino acid. Also provided are conjugates comprising said peptide, pharmaceutical compositions comprising said peptide or said conjugates, and uses of said peptide, conjugate or composition, for example, in the treatment, imaging and/or diagnosis of an ανβ6- expressing tumour in a mammalian subject.

  本发明提供了一种选择性结合ανβ6整合素的肽，该肽具有氨基酸序列，包括基序X1BnRGDLX2X3X4 ZmX5，其中X1是任何D-氨基酸，Bn是任何n个氨基酸的序列，可以是天然的或非天然的，D-或L-，可以相同也可以不同，其中n是1到10之间的数字，X2和X3分别选自任何氨基酸，X4是Leu或Ile，Zm是任何m个氨基酸的序列，可以是天然的或非天然的，D-或L-，可以相同也可以不同，其中m是1到10之间的数字，X5是任何L-或D-氨基酸。还提供了包括所述肽的结合物，包括所述肽或所述结合物的药物组合物，以及所述肽，结合物或组合物的用途，例如，在治疗、成像和/或诊断哺乳动物主体中表达ανβ6的肿瘤。
• Synthesis and biological evaluation of <i>S</i>-lipidated lipopeptides of a connexin 43 channel inhibitory peptide
  作者：Sung-Hyun Yang、Connor A. Clemett、Margaret A. Brimble、Simon J. O'Carroll、Paul W. R. Harris

  DOI：10.1039/d0md00172d

  日期：——

  The synthesis and biological activity of 42 novel S-lipidated analogues of a connexin 43 channel inhibitory Peptide5 is described. Unmodified Peptide5 moderates hemichannels and gap junctions that are both implicated in the progression of neurological disease. Peptide5 was site-specifically modified with a cysteine residue, which then underwent thiol–ene mediated S-lipidation to afford S-lipidated

  描述了连接蛋白43通道抑制肽5的42种新的S脂质类似物的合成和生物学活性。未修饰的Peptide5调节与神经疾病发展有关的半通道和间隙连接。用半胱氨酸残基对Peptide5进行位点特异性修饰，然后对其进行硫醇-烯介导的S-脂化作用，得到含有直链，支链或芳族脂质的S-脂化的Peptide5类似物。评估修饰的肽对半通道开放的作用，并在血清稳定性研究中评估最有希望的候选物。
• Synthesis and Systematic Study on the Effect of Different PEG Units on Stability of PEGylated, Integrin-αvβ6-Specific A20FMDV2 Analogues in Rat Serum and Human Plasma
  作者：Kuo-yuan Hung、Renata Kowalczyk、Ami Desai、Margaret A. Brimble、John F. Marshall、Paul W. R. Harris

  DOI：10.3390/molecules27144331

  日期：——

  incorporation of poly (ethylene glycol) chains, coined PEGylation, is a well-established approach to improve the pharmacokinetic properties of drug molecules. Here, we report a systematic study on the incorporation of a varying number of ethylene glycol units (1–20) into the A20FMDV2 peptide to establish the effects of PEGylation size on the peptide stability in both rat serum and human plasma. In addition

  A20FMDV2 是一种 20 聚体肽，对肿瘤相关的 αvβ6 整联蛋白表现出高选择性和亲和力，可以与细胞外配体竞争关键的 RGD 结合位点，作为一种有前景的 αvβ6 特异性抑制剂用于抗癌治疗。不幸的是，A20FMDV2 的临床价值受到快速肾脏排泄导致的血液半衰期较短以及据报道对血清蛋白酶高度敏感性的限制。聚乙二醇链的掺入，即聚乙二醇化，是改善药物分子药代动力学特性的一种行之有效的方法。在此，我们报告了一项关于将不同数量的乙二醇单元 (1-20) 掺入 A20FMDV2 肽中的系统研究，以确定聚乙二醇化大小对大鼠血清和人血浆中肽稳定性的影响。此外，还描述了乙酰基和丙酰基聚乙二醇化处理对肽稳定性的影响。对所选肽类似物的整合素-αvβ6 靶向结合进行了评估，显示出良好的体外特异性和活性。大鼠血清中的稳定性研究表明，所有聚乙二醇化肽都表现出良好的稳定性，并且含有二十个乙二醇单元（PEG 20
• Synthesis of truncated analogues of preptin-(1–16), and investigation of their ability to stimulate osteoblast proliferation
  作者：Renata Kowalczyk、Sung H. Yang、Margaret A. Brimble、Karen E. Callon、Maureen Watson、Young-Eun Park、Jillian Cornish

  DOI：10.1016/j.bmc.2014.05.026

  日期：2014.7

  Preptin, a 34-amino acid residue peptide hormone is co-secreted with insulin from the β-pancreatic cells and is active in fuel metabolism. We have previously established that a shorter fragment of preptin, namely preptin-(1–16), stimulates bone growth by proliferation and increasing the survival rate of osteoblasts. This was demonstrated in both in vitro and in vivo models. These findings suggest that preptin-(1–16) could play an important role in the anabolic therapy of osteoporosis. However, due to the large size of the peptide it is not an ideal therapeutic agent. The aim of this study was to identify the shortest preptin analogue that retains or even increases the bone anabolic activity as compared to the parent preptin-(1–16) peptide. Truncations were made in a methodical manner from both the N-terminus and the C-terminus of the peptide, and the effect of these deletions on the resulting biological activity was assessed. In order to improve the enzymatic stability of the shortest yet active analogue identified, ruthenium-catalysed ring closing metathesis was used to generate a macrocyclic peptide using allylglycine residues as handles for ring formation. We have successfully identified a short 8-amino acid preptin (1–8) fragment that retains an anabolic effect on the proliferation of primary rat osteoblasts and enhances bone nodule formation. Preptin (1–8) is a useful lead compound for the development of orally active therapeutics for the treatment of osteoporosis.