(S)-6-amino-2-((S)-2-((S)-2-((S)-2-((S)-2-amino-3-hydroxypropanamido)-5-guanidinopentanamido)-3-(1H-imidazol-5-yl)propanamido)-3-(1H-indol-3-yl)propanamido)-N-((S)-1-(((S)-1-amino-4-methyl-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)hexanamide | 1215185-13-9

• 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
• 英文名称: (S)-6-amino-2-((S)-2-((S)-2-((S)-2-((S)-2-amino-3-hydroxypropanamido)-5-guanidinopentanamido)-3-(1H-imidazol-5-yl)propanamido)-3-(1H-indol-3-yl)propanamido)-N-((S)-1-(((S)-1-amino-4-methyl-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)hexanamide
• CAS: 1215185-13-9
• 化学式: C₄₇H₆₉N₁₅O₈
• 分子量: 972.161
• InChiKey: IVGKBAIZJZKJBR-YRVFCXMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.93
• 重原子数：
  70.0
• 可旋转键数：
  30.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  396.33
• 氢给体数：
  15.0
• 氢受体数：
  12.0

反应信息

• 作为产物：
  描述：

  Ac-GASRHWKFL-NH₂ 在 Ni(II) 作用下， 生成 (S)-6-amino-2-((S)-2-((S)-2-((S)-2-((S)-2-amino-3-hydroxypropanamido)-5-guanidinopentanamido)-3-(1H-imidazol-5-yl)propanamido)-3-(1H-indol-3-yl)propanamido)-N-((S)-1-(((S)-1-amino-4-methyl-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)hexanamide
  参考文献：
  名称：

  Sequence-Specific Ni(II)-Dependent Peptide Bond Hydrolysis for Protein Engineering. Combinatorial Library Determination of Optimal Sequences

  摘要：

  Previously we demonstrated for several examples that peptides having a general internal sequence R-N-Yaa-Ser/Thr-Xaa-His-Zaa-R-C (Yaa = Glu or Ala, Xaa = Ala or His, Zaa = Lys, R-N and R-C = any N- and C-terminal amino acid sequence) were hydrolyzed specifically at the Yaa-Ser/Thr peptide bond in the presence of Ni(II) ions at alkaline pH (Krezel, A.; Mylonas, M.; Kopera, E.; Bal, E. Acta Biochim. Polon. 2006, 53, 721-727 and references therein). Hereby we report the synthesis of a combinatorial library of CH3CO-Gly-Ala-(Ser/Thr)-Xaa-His-Zaa-Lys-Phe-Leu-NH2 peptides, where Xaa residues included 17 common alpha-amino acids (except Asp, Glu, and Cys) and Zaa residues included 19 common alpha-amino acids (except Cys). The Ni(II)-dependent hydrolysis at 37 and 45 degrees C of batches of combinatorial peptide mixtures randomized at Zaa was monitored by MALDI-TOF mass spectrometry. The correctness of library-based predictions was confirmed by accurate measurements of hydrolysis rates of seven selected peptides using HPLC. The hydrolysis was strictly limited to the Ala-Ser/Thr bond in all library and individual peptide experiments. The effects of individual residues on hydrolysis rates were quantified and correlated with physical properties of their side chains according to a model of independent contributions of Xaa and Zaa residues. The principal component analysis calculations demonstrated partial molar side chain volume and the free energy of amino acid vaporization for both Xaa and Zaa residues and the amine pK(a) for Zaa residues to be the most significant empirical parameters influencing the hydrolysis rate. Therefore, efficient hydrolysis required bulky and hydrophobic residues at both variable positions Xaa and Zaa, which contributed independently to the hydrolysis rate. This relationship between the peptide sequence and the hydrolysis rate provides a basis for further research, aimed at the elucidation of the reaction mechanism and biotechnological applications of Ni(II)-dependent peptide bond hydrolysis.

  DOI：

  10.1021/ja907567r

文献信息

• Development of a Chemical Methodology for the Preparation of Peptide Thioesters Applicable to Naturally Occurring Peptides Using a Sequential Quadruple Acyl Transfer System
  作者：Yusuke Tsuda、Akira Shigenaga、Kohei Tsuji、Masaya Denda、Kohei Sato、Keisuke Kitakaze、Takahiro Nakamura、Tsubasa Inokuma、Kohji Itoh、Akira Otaka

  DOI：10.1002/open.201500086

  日期：2015.8

  thioesters using innovative methodology that features nickel(II)‐mediated alcoholysis of a naturally occurring peptide sequence, followed by O−N and N−S acyl transfers. This protocol involves sequential quadruple acyl transfer, termed SQAT. Notably, the SQAT system consists of sequential chemical reactions that allow naturally occurring peptide sequences to be converted to thioesters without requiring an

  肽硫酯在蛋白质化学中非常有用，基于化学和生物化学的方案可用于制备硫酯。在这些方案中，只有少数几种基于生物化学的方法已用于天然存在的肽序列。适用于自然序列的基于化学方法的开发仍然是一个挑战，而此类方法的开发将对蛋白质科学做出重大贡献。在这里，我们描述了使用创新方法制备肽硫酯的方法，该方法具有天然存在的肽序列的镍（II）介导的醇解作用，然后进行ON和N-S酰基转移。该协议涉及顺序的四重酰基转移，称为SQAT。尤其，
• Effect of <scp>d</scp>-Amino Acid Substitutions on Ni(II)-Assisted Peptide Bond Hydrolysis
  作者：Hanieh H. Ariani、Agnieszka Polkowska-Nowakowska、Wojciech Bal

  DOI：10.1021/ic3022672

  日期：2013.3.4

  Previously we demonstrated the sequence-specific hydrolysis of the R-1-(Ser/Thr)-peptide bond in Ni(II) complexes of peptides with a general R-1-(Ser/Thr)-Xaa-His-Zaa-R-2 sequence (R-1 and R-2 being any sequences) (Kopera, E.; Krezel, A.; Protas, A. M.; Belczyk, A.; Bonna, A.; Wyslouch-Cieszynska, A.; Poznanski, J.; Bal, W. Inorg. Chem. 2010, 49, 6636). In order to refine our understanding of the mechanism of this reaction and to find ways to accelerate it, we undertook a systematic study of effects of D-amino acid substitutions in the template Ac-Gly-Ala-Ser-Arg-His-Trp-Lys-Phe-Leu-NH2 peptide on the hydrolysis rate constants. We found that all stereochemical alterations made around the Ni(II) chelate plane resulted in the decrease of the reaction rate. However, the Ni(II) coordination, a prerequisite to the reaction, was not compromised by these substitutions. We demonstrated that the reaction is only possible when either the side chain of the crucial Ser (or Thr) residue is on the same part of the chelate plane as the next residue in the sequence (Arg), or the side chain of the residue following His (Trp) resides on the opposite side of the plane. The rate of reaction is the fastest when both these conditions are fulfilled. Another novel effect is the strong dependence of the rate of the acyl shift step on the character of the leaving group.