Fmoc-D-Ser-O^tBu | 225662-91-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-D-Ser-O^tBu
• 英文别名: tert-Butyl (((9H-fluoren-9-yl)methoxy)carbonyl)-D-serinate；tert-butyl (2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-hydroxypropanoate
• CAS: 225662-91-9
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: ZYOWIDHANLLHNO-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Fmoc-D-Ser-O^tBu 在 四溴化碳 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (2S,6S)-N²,N⁶-bis(fluoren-9-ylmethoxycarbonyl)lanthionine α-allyl ester
  参考文献：
  名称：

  Lipolanthionine Peptides Act as Inhibitors of TLR2-Mediated IL-8 Secretion. Synthesis and Structure−Activity Relationships

  摘要：

  Lipoproteins from Gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers. For this reason, these compounds constitute highly active adjuvants for vaccines either admixed or covalently linked. The lanthionine scaffold has structural similarity with the S-(2,3-dihydroxypropyl)cysteine core structure of the lipopeptides. Therefore, lanthionine-based lipopeptide amides were synthesized and probed for activity as potential TLR2 agonists or antagonists. A collection of analytically defined lipolanthionine peptide amides exhibited an inhibitory effect of the TLR2-mediated IL-8 secretion when applied in high molar excess to the agonistic synthetic lipopeptide Pam(3)Cys-Ser-(LyS)(4)-OH. Structure-activity relationships revealed the influence of the chirality of the two alpha-carbon atoms, the chain lengths of the attached fatty acids and fatty amines, and the oxidation level of the sulfur atom on the inhibitory activity of the lipolanthionine peptide amides.

  DOI：

  10.1021/jm050585d
• 作为产物：
  描述：

  Fmoc-D-丝氨酸 、 叔丁醇 在 copper(l) chloride 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 124.0h， 以55.5%的产率得到Fmoc-D-Ser-O^tBu
  参考文献：
  名称：

  Lipolanthionine Peptides Act as Inhibitors of TLR2-Mediated IL-8 Secretion. Synthesis and Structure−Activity Relationships

  摘要：

  Lipoproteins from Gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers. For this reason, these compounds constitute highly active adjuvants for vaccines either admixed or covalently linked. The lanthionine scaffold has structural similarity with the S-(2,3-dihydroxypropyl)cysteine core structure of the lipopeptides. Therefore, lanthionine-based lipopeptide amides were synthesized and probed for activity as potential TLR2 agonists or antagonists. A collection of analytically defined lipolanthionine peptide amides exhibited an inhibitory effect of the TLR2-mediated IL-8 secretion when applied in high molar excess to the agonistic synthetic lipopeptide Pam(3)Cys-Ser-(LyS)(4)-OH. Structure-activity relationships revealed the influence of the chirality of the two alpha-carbon atoms, the chain lengths of the attached fatty acids and fatty amines, and the oxidation level of the sulfur atom on the inhibitory activity of the lipolanthionine peptide amides.

  DOI：

  10.1021/jm050585d

文献信息

• Structural Revision of Natural Cyclic Depsipeptide MA026 Established by Total Synthesis and Biosynthetic Gene Cluster Analysis
  作者：Chihiro Uchiyama、Akane Fukuda、Minagi Mukaiyama、Yoshiki Nakazawa、Yuka Kuramochi、Kyohei Muguruma、Mitsue Arimoto、Akihiro Ninomiya、Koichiro Kako、Yohei Katsuyama、Sho Konno、Akihiro Taguchi、Kentaro Takayama、Atsuhiko Taniguchi、Yoko Nagumo、Takeo Usui、Yoshio Hayashi

  DOI：10.1002/anie.202015193

  日期：2021.4.12

  previously reported in that two amino acid residues, assigned in error, have been replaced. Synthesized MA026 with the revised structure showed a tight junction (TJ) opening activity like that of the natural one in a cell‐based TJ opening assay. Bioinformatic analysis of the putative MA026 biosynthetic gene cluster (BGC) of RtIB026 demonstrated that the stereochemistry of each amino acid residue in the

  从假单胞菌中分离的天然 14 聚体环状缩肽 MA026 的修订结构sp. RtlB026 于 2002 年通过 HPLC、MS/MS 和 NMR 的理化分析建立，并通过全固相合成证实。修改后的结构与先前报道的不同，其中两个错误分配的氨基酸残基已被替换。具有修改结构的合成 MA026 显示出紧密连接 (TJ) 开放活动，就像基于细胞的 TJ 开放分析中的天然开放活动一样。对 RtIB026 的推定 MA026 生物合成基因簇 (BGC) 的生物信息学分析表明，可以合理解释修订结构中每个氨基酸残基的立体化学。使用 xantholysin BGC 进行的系统发育分析表明 xantholysin 和 MA026 之间具有异常高的同源性（约 90%）。
• Peptides Containing <i>meso</i> ‐Oxa‐Diaminopimelic Acid as Substrates for the Cell‐Shape‐Determining Proteases Csd6 and Pgp2
  作者：Arvind S. Soni、Chang Sheng‐Huei Lin、Michael E. P. Murphy、Martin E. Tanner

  DOI：10.1002/cbic.201900011

  日期：2019.6.14

  tetrapeptide substrate. The isosteric analogue meso-oxa-Dap was utilized in place of meso-Dap to simplify the synthetic procedure. The more efficient synthesis involved ring opening of a peptide-embedded aziridine by a serine-based nucleophile. A branched tetrapeptide was also prepared as a mimic of the terminus of a crosslinked PG tetrapeptide. We used MS analysis to demonstrate that the tripeptide serves

  Csd6和Pgp2酶分别是在病原菌幽门螺杆菌和空肠弯曲菌中发现的肽聚糖（PG）蛋白酶。这些酶参与非交联的PG侧链的修饰，并催化内消旋二氨基庚二酸（meso-Dap）和d-丙氨酸之间的键的断裂，从而将PG四肽转化为PG三肽。众所周知，它们是决定细胞形状的酶，因为相应基因的缺失会导致突变菌株失去正常的螺旋表型，而是具有直杆形态。在这项工作中，我们报告了针对三肽底物Ac-iso-d-Glu-meso-oxa-Dap-d-Ala的合成的两种方法，该方法可模拟非交联的PG四肽底物的末端。等规类似物meso-oxa-Dap代替了meso-Dap来简化合成过程。更有效的合成涉及通过基于丝氨酸的亲核试剂使包埋有肽的氮丙啶开环。还制备了支链四肽，以模拟交联的PG四肽的末端。我们使用MS分析来证明三肽既可作为Csd6和Pgp2的底物，支链四肽也可作为Pgp2的底物，尽管其速率要慢得多。
• A Novel and Efficient Route towards α-GalNAc-Ser and α-GalNAc-Thr Building Blocks for Glycopeptide Synthesis
  作者：Gottfried A. Winterfeld、Yukishige Ito、Tomoya Ogawa、Richard R. Schmidt

  DOI：10.1002/(sici)1099-0690(199905)1999:5<1167::aid-ejoc1167>3.0.co;2-2

  日期：1999.5
• Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis
  作者：Yalong Zhang、Saddam M. Muthana、David Farnsworth、Olaf Ludek、Kristie Adams、Joseph J. Barchi、Jeffrey C. Gildersleeve

  DOI：10.1021/ja212188r

  日期：2012.4.11

  Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.
• Lipolanthionine Peptides Act as Inhibitors of TLR2-Mediated IL-8 Secretion. Synthesis and Structure−Activity Relationships
  作者：Tobias Seyberth、Söhnke Voss、Roland Brock、Karl-Heinz Wiesmüller、Günther Jung

  DOI：10.1021/jm050585d

  日期：2006.3.1

  Lipoproteins from Gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers. For this reason, these compounds constitute highly active adjuvants for vaccines either admixed or covalently linked. The lanthionine scaffold has structural similarity with the S-(2,3-dihydroxypropyl)cysteine core structure of the lipopeptides. Therefore, lanthionine-based lipopeptide amides were synthesized and probed for activity as potential TLR2 agonists or antagonists. A collection of analytically defined lipolanthionine peptide amides exhibited an inhibitory effect of the TLR2-mediated IL-8 secretion when applied in high molar excess to the agonistic synthetic lipopeptide Pam(3)Cys-Ser-(LyS)(4)-OH. Structure-activity relationships revealed the influence of the chirality of the two alpha-carbon atoms, the chain lengths of the attached fatty acids and fatty amines, and the oxidation level of the sulfur atom on the inhibitory activity of the lipolanthionine peptide amides.