TAYFLLALAGRW-NH2

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: TAYFLLALAGRW-NH2
• 英文别名: H-Thr-Ala-Tyr-Phe-Leu-Leu-Ala-Leu-Ala-Gly-Arg-Trp-NH2；(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-N-[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]-4-methylpentanamide
• 化学式: C₆₈H₁₀₁N₁₇O₁₄
• 分子量: 1380.66
• InChiKey: AEBDTXYNZJFBTQ-OYZRLRPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  99
• 可旋转键数：
  40
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  510
• 氢给体数：
  18
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  Fmoc-L-丙氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-O-叔丁基-L-苏氨酸 、 NΑ-FMOC-NΩ-(2,2,5,7,8-五甲基苯并二氢吡喃-6-磺酰基)-L-精氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成 TAYFLLALAGRW-NH2
  参考文献：
  名称：

  Sequence-Based Design and Discovery of Peptide Inhibitors of HIV-1 Integrase:  Insight into the Binding Mode of the Enzyme

  摘要：

  Integration of viral DNA into the host chromosome is an essential step in the HIV life cycle. This process is mediated by integrase (IN), a 32 kDa viral enzyme that has no mammalian counterpart, rendering it an attractive target for antiviral drug design. Herein, we present a novel approach toward elucidating "hot spots" of protein-protein or protein-nucleic acid interactions of IN through the design of peptides that encompass conserved amino acids and residues known to be important for enzymatic activity. We designed small peptides (7 - 17 residues) containing at least one amino acid residue that is important for IN catalytic activities (3'-processing and strand transfer) or viral replication. All these peptides were synthesized on solid phase by fluorenylmethoxycarbonyl (Fmoc) chemistry and evaluated for their inhibition of IN catalytic activities. Such specific sites of interest (i.e., protein-DNA or protein-drug interactions) could potentially be used as drug targets. This novel "sequence walk" strategy across the entire 288 residues of IN has allowed the identification of two peptides NL-6 and NL-9 with 50% inhibitory concentration (IC50) values of 2.7 and 56 AM for strand transfer activity, respectively. Amino acid substitution analysis on these peptides revealed essential residues for activity, and the rational truncation of NL-6 produced a novel hexapeptide (peptide NL6-5) with inhibitory potency equal to that of the parent dodecapeptide (peptide NL-6). More significantly, the retroinverso analogue of NL-6 (peptide RDNL-6) in which the direction of the sequence is reversed and the chirality of each amino acid residue is inverted displayed improved inhibitory potency against 3'-processing of HIV-1 IN by 6-fold relative to the parent NL-6, serving as a metabolically stable derivative for further in vitro and in vivo analyses.

  DOI：

  10.1021/jm060307u

文献信息

• Sequence-Based Design and Discovery of Peptide Inhibitors of HIV-1 Integrase:  Insight into the Binding Mode of the Enzyme
  作者：Hui-Yuan Li、Zahrah Zawahir、Lai-Dong Song、Ya-Qiu Long、Nouri Neamati

  DOI：10.1021/jm060307u

  日期：2006.7.1

  Integration of viral DNA into the host chromosome is an essential step in the HIV life cycle. This process is mediated by integrase (IN), a 32 kDa viral enzyme that has no mammalian counterpart, rendering it an attractive target for antiviral drug design. Herein, we present a novel approach toward elucidating "hot spots" of protein-protein or protein-nucleic acid interactions of IN through the design of peptides that encompass conserved amino acids and residues known to be important for enzymatic activity. We designed small peptides (7 - 17 residues) containing at least one amino acid residue that is important for IN catalytic activities (3'-processing and strand transfer) or viral replication. All these peptides were synthesized on solid phase by fluorenylmethoxycarbonyl (Fmoc) chemistry and evaluated for their inhibition of IN catalytic activities. Such specific sites of interest (i.e., protein-DNA or protein-drug interactions) could potentially be used as drug targets. This novel "sequence walk" strategy across the entire 288 residues of IN has allowed the identification of two peptides NL-6 and NL-9 with 50% inhibitory concentration (IC50) values of 2.7 and 56 AM for strand transfer activity, respectively. Amino acid substitution analysis on these peptides revealed essential residues for activity, and the rational truncation of NL-6 produced a novel hexapeptide (peptide NL6-5) with inhibitory potency equal to that of the parent dodecapeptide (peptide NL-6). More significantly, the retroinverso analogue of NL-6 (peptide RDNL-6) in which the direction of the sequence is reversed and the chirality of each amino acid residue is inverted displayed improved inhibitory potency against 3'-processing of HIV-1 IN by 6-fold relative to the parent NL-6, serving as a metabolically stable derivative for further in vitro and in vivo analyses.