Ac-SQAVLPDDFPRY-NH₂ | 1613467-25-6

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: Ac-SQAVLPDDFPRY-NH₂
• 英文别名: Ac-Ser-Gln-Ala-Val-Leu-Pro-Asp-Asp-Phe-Pro-Arg-Tyr-NH2；(3S)-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-5-amino-5-oxopentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-4-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid
• CAS: 1613467-25-6
• 化学式: C₆₆H₉₇N₁₇O₂₀
• 分子量: 1448.6
• InChiKey: OJAOQCQCQBMHSB-RZRMTEMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  103
• 可旋转键数：
  41
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  597
• 氢给体数：
  18
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  Fmoc-L-缬氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-丙氨酸 、 Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 乙酸酐 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-L-谷氨酰胺 、 Fmoc-Pbf-L-精氨酸 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 N,N-二甲基甲酰胺 为溶剂， 反应 2.06h， 以15 mg的产率得到Ac-SQAVLPDDFPRY-NH₂
  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

• 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.