S-<(benzyloxycarbonyl)glycyl>-N-acetylcystamine | 104071-89-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: S-<(benzyloxycarbonyl)glycyl>-N-acetylcystamine
• 英文别名: S-[(benzyloxycarbonyl)glycyl]-N-acetylcystamine
• CAS: 104071-89-8
• 化学式: C₁₄H₁₈N₂O₄S
• 分子量: 310.374
• InChiKey: ZTMNRAAEFVBWKM-UHFFFAOYSA-N

物化性质

• 沸点：
  552.2±45.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  21.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.5
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  S-<(benzyloxycarbonyl)glycyl>-N-acetylcystamine 在 氢溴酸 、 溶剂黄146 作用下， 反应 0.5h， 以90%的产率得到S-glycyl-N-acetylcysteamine hydrobromide
  参考文献：
  名称：

  Synthesis and radioprotective activity of new cysteamine and cystamine derivatives

  摘要：

  A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting compounds of this series was N-glycyl-S-acetylcysteamine trifluoroacetate (16, I 102). Structure-activity relationships are discussed.

  DOI：

  10.1021/jm00161a015
• 作为产物：
  描述：

  N-乙酰基半胱胺 、 N-苄氧羰基甘氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 以57%的产率得到S-<(benzyloxycarbonyl)glycyl>-N-acetylcystamine
  参考文献：
  名称：

  Biomimetic Catalysis of Intermodular Aminoacyl Transfer

  摘要：

  Intermodular aminoacyl transfer is the fundamental bond-forming reaction in the biosynthesis of polypeptides by ribosomes and nonribosomal peptide synthetases (NRPS). Here we report the design and functional characterizations of short synthetic alpha-helical peptides that mimic the aminoacyl loading and intermodular aminoacyl transfer steps of NRPS with aminolysis rate enhancements in neutral aqueous solutions of up to 5400-fold (k(cat)/k(uncat)). The catalysts operate as noncovalently associated peptide assemblies with composite active sites fashioned at the interface between helical subunits. Following the substrate loading at the active site cysteine, the juxtaposition of the resulting aminoacyl thiolester and the nucleophilic amine of the acyl acceptor moiety gives rise to high effective concentrations (up to 54 M) that facilitate interhelical aminoacyl transfer with rates typically exceeding 10(-4) sec(-1). Moreover, studies based on homo- and heteromeric assemblies, active site amino acid substitutions, kinetic analysis, and reaction modeling indicate that the de novo designed supramolecular catalysts reported herein exhibit some of the basic characteristics of natural enzymes, including precise positioning and pK(a) modulation of active site residues, covalent catalysis, and multiple product turnovers.

  DOI：

  10.1021/ja067124h

文献信息

• Functional and Mechanistic Analyses of Biomimetic Aminoacyl Transfer Reactions in de Novo Designed Coiled Coil Peptides via Rational Active Site Engineering
  作者：Luke J. Leman、Dana A. Weinberger、Zheng-Zheng Huang、Keith M. Wilcoxen、M. Reza Ghadiri

  DOI：10.1021/ja068052x

  日期：2007.3.1

  Ribosomes and nonribosomal peptide synthetases (NRPSs) carry out instructed peptide synthesis through a series of directed intermodular aminoacyl transfer reactions. We recently reported the design of coiled-coil assemblies that could functionally mimic the elementary aminoacyl loading and intermodular aminoacyl transfer steps of NRPSs. These peptides were designed initially to accelerate aminoacyl transfer mainly through catalysis by approximation by closely juxtaposing four active site moieties, two each from adjacent noncovalently associated helical modules. In our designs peptide self-assembly positions a cysteine residue that is used to covalently capture substrates from solution via transthiolesterification (substrate loading step to generate the aminoacyl donor site) adjacent to an aminoacyl acceptor site provided by a covalently tethered amino acid or modeled by the epsilon-amine of an active site lysine. However, through systematic functional analyses of 48 rationally designed peptide sequences, we have now determined that the substrate loading and intermodular aminoacyl transfer steps can be significantly influenced (up to similar to 10(3)-fold) by engineering changes in the active site microenvironment through amino acid substitutions and variations in the inter-residue distances and geometry. Mechanistic studies based on N-15 NMR and kinetic analysis further indicate that certain active site constellations furnish an unexpectedly large pK(a) depression (1.5 pH units) of the aminoacyl-acceptor moiety, helping to explain the observed high rates of aminoacyl transfer in those constructs. Taken together, our studies demonstrate the feasibility of engineering efficient de novo peptide sequences possessing active sites and functions reminiscent of those in natural enzymes.