Ac-FTLDADF

• 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: Ac-FTLDADF
• 英文别名: (S)-3-[(S)-2-((S)-2-{(S)-2-[(2S,3R)-2-((S)-2-Acetylamino-3-phenyl-propionylamino)-3-hydroxy-butyrylamino]-4-methyl-pentanoylamino}-3-carboxy-propionylamino)-propionylamino]-N-((S)-1-carboxy-2-phenyl-ethyl)-succinamic acid；(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-4-[[(1S)-1-carboxy-2-phenylethyl]amino]-4-oxobutanoic acid
• 化学式: C₄₁H₅₅N₇O₁₄
• 分子量: 869.926
• InChiKey: CCECJWGXUJRVOU-FPLQQAKMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  62
• 可旋转键数：
  25
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  336
• 氢给体数：
  11
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  乙酸酐 、 FTLDADF 生成 Ac-FTLDADF
  参考文献：
  名称：

  R2 C-terminal peptide inhibition of mammalian and yeast ribonucleotide reductase

  摘要：

  Eucaryotic ribonucleotide reductases (RR) catalyze the reduction of ribonucleoside diphosphates to 2'-deoxyribonucleoside diphosphates. Each has an R1(2)R2(2) quaternary structure with each subunit playing a critical role in catalysis. Separation of the subunits results in loss of activity. Previous studies have demonstrated that peptides corresponding to the C-terminus of R2 disrupt subunit association by competion with R2 and have potential usefulness as therapeutics. Extensive structure-function studies have been carried out on peptide inhibition of herpes simplex RR in an effort to develop antiviral agents based on the observation that the herpes simplex R2 C-terminus, YAGAVVNDL, is quite different from the corresponding mammalian sequence. In this work we report a detailed structure-function analysis of peptide inhibition of mammalian and, to a more limited extent, Saccharomyces cerevisiae RRs. Our results for mammalian RR support the following conclusions with regard to the effect of substitution on inhibitory potency: (a) the N-acetylated R2 C-terminal heptapeptide N-AcPhe(384)Thr(385)Leu(386)Asp(387)Ala(388)Asp(389)Phe(390) (N-AcF(7)TLDADF(1)) is the minimal core peptide length required; deletion of the N-terminus or of middle positions (resulting in penta- and hexapeptides) results in large losses in inhibitory potency; (b) a free carboxylate is required on the C-terminal Phe; (c) Phe is strongly preferred to Leu in positions 1 and 7 and a bulky aliphatic group is preferred in position 5; (d) neither negative charge in positions 2 or 4 nor a polar side chain in position 6 are required for peptide binding, contrary to what evolutionary patterns in the R2 C-terminus of RR would suggest. S. cerevisiae RR displays a similar length dependence on the corresponding N-acetylated R2 C-terminal heptapeptide, N-AcFTFNEDF. This peptide has a 4-fold higher inhibitory potency toward S. cerevisiae RR than toward mammalian RR. Such selectivity raises the possibility that peptide analogs related to R2 C-termini can be developed as therapeutic agents even against organisms having R2 C-terminal sequences similar to that of mammalian RR.

  DOI：

  10.1021/jm00076a015

文献信息

• R2 C-terminal peptide inhibition of mammalian and yeast ribonucleotide reductase
  作者：Alison Fisher、Fu De Yang、Harvey Rubin、Barry S. Cooperman

  DOI：10.1021/jm00076a015

  日期：1993.11

  Eucaryotic ribonucleotide reductases (RR) catalyze the reduction of ribonucleoside diphosphates to 2'-deoxyribonucleoside diphosphates. Each has an R1(2)R2(2) quaternary structure with each subunit playing a critical role in catalysis. Separation of the subunits results in loss of activity. Previous studies have demonstrated that peptides corresponding to the C-terminus of R2 disrupt subunit association by competion with R2 and have potential usefulness as therapeutics. Extensive structure-function studies have been carried out on peptide inhibition of herpes simplex RR in an effort to develop antiviral agents based on the observation that the herpes simplex R2 C-terminus, YAGAVVNDL, is quite different from the corresponding mammalian sequence. In this work we report a detailed structure-function analysis of peptide inhibition of mammalian and, to a more limited extent, Saccharomyces cerevisiae RRs. Our results for mammalian RR support the following conclusions with regard to the effect of substitution on inhibitory potency: (a) the N-acetylated R2 C-terminal heptapeptide N-AcPhe(384)Thr(385)Leu(386)Asp(387)Ala(388)Asp(389)Phe(390) (N-AcF(7)TLDADF(1)) is the minimal core peptide length required; deletion of the N-terminus or of middle positions (resulting in penta- and hexapeptides) results in large losses in inhibitory potency; (b) a free carboxylate is required on the C-terminal Phe; (c) Phe is strongly preferred to Leu in positions 1 and 7 and a bulky aliphatic group is preferred in position 5; (d) neither negative charge in positions 2 or 4 nor a polar side chain in position 6 are required for peptide binding, contrary to what evolutionary patterns in the R2 C-terminus of RR would suggest. S. cerevisiae RR displays a similar length dependence on the corresponding N-acetylated R2 C-terminal heptapeptide, N-AcFTFNEDF. This peptide has a 4-fold higher inhibitory potency toward S. cerevisiae RR than toward mammalian RR. Such selectivity raises the possibility that peptide analogs related to R2 C-termini can be developed as therapeutic agents even against organisms having R2 C-terminal sequences similar to that of mammalian RR.