Fmoc-Ala-(R-HB)2-OtBu | 233258-56-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Ala-(R-HB)2-OtBu
• 英文别名: Fmoc-Ala-ObAla(3R-Me)-ObAla(3R-Me)-OtBu；tert-butyl (3R)-3-[(3R)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoyl]oxybutanoyl]oxybutanoate
• CAS: 233258-56-5
• 化学式: C₃₀H₃₇NO₈
• 分子量: 539.626
• InChiKey: KAKKBHWZPYONIO-AQNXPRMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Fmoc-Ala-(R-HB)2-OtBu 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以100%的产率得到Fmoc-Ala-(R-HB)2-OH
  参考文献：
  名称：

  Nonapeptide Analogues Containing (R)-3-Hydroxybutanoate and β-Homoalanine Oligomers:  Synthesis and Binding Affinity to a Class I Major Histocompatibility Complex Protein

  摘要：

  Crystal structures of antigenic peptides bound to class I MHC proteins suggest that chemical modifications of the central part of the bound peptide should not alter binding affinity to the MHC restriction protein but could perturb the T-cell response to the parent epitope. In our effort in designing nonpeptidic high-affinity ligands for class I MHC proteins, oligomers of (R)-3-hydroxybutanoate and(or) beta-homoalanine have been substituted for the central part of a HLA-B27-restricted T-cell epitope of viral origin. The affinity of six modified peptides to the B*2705 allele was determined by an in vitro stabilization assay. Four out of the six designed analogues presented an affinity similar to that of the parent peptide. Two compounds, sharing the same stereochemistry (R,R,S,S) at the four stereogenic centers of the nonpeptidic spacer, bound to B*2705 with a 5-6-fold decreased affinity. Although the chiral spacers do not strongly interact with the protein active site, there are configurations which are not accepted by the MHC binding groove, probably because of improper orientation of some lateral substituents in the bound state and different conformational behavior in the free state, However we demonstrate that beta-amino acids can be incorporated in the sequence of viral T-cell epitopes without impairing MHC binding. The presented structure-activity relationships open the door to the rational design of peptide-based vaccines and of nonnatural T-cell receptor antagonists aimed at blocking peptide-specific T-cell responses in MHC-associated autoimmune diseases.

  DOI：

  10.1021/jm981123l
• 作为产物：
  描述：

  Fmoc-L-丙氨酸 、 (3R)-3-<<(3'R)-3'-hydroxybutanoyl>oxy>butanoic acid tert-butyl ester 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以30%的产率得到Fmoc-Ala-(R-HB)2-OtBu
  参考文献：
  名称：

  Nonapeptide Analogues Containing (R)-3-Hydroxybutanoate and β-Homoalanine Oligomers:  Synthesis and Binding Affinity to a Class I Major Histocompatibility Complex Protein

  摘要：

  Crystal structures of antigenic peptides bound to class I MHC proteins suggest that chemical modifications of the central part of the bound peptide should not alter binding affinity to the MHC restriction protein but could perturb the T-cell response to the parent epitope. In our effort in designing nonpeptidic high-affinity ligands for class I MHC proteins, oligomers of (R)-3-hydroxybutanoate and(or) beta-homoalanine have been substituted for the central part of a HLA-B27-restricted T-cell epitope of viral origin. The affinity of six modified peptides to the B*2705 allele was determined by an in vitro stabilization assay. Four out of the six designed analogues presented an affinity similar to that of the parent peptide. Two compounds, sharing the same stereochemistry (R,R,S,S) at the four stereogenic centers of the nonpeptidic spacer, bound to B*2705 with a 5-6-fold decreased affinity. Although the chiral spacers do not strongly interact with the protein active site, there are configurations which are not accepted by the MHC binding groove, probably because of improper orientation of some lateral substituents in the bound state and different conformational behavior in the free state, However we demonstrate that beta-amino acids can be incorporated in the sequence of viral T-cell epitopes without impairing MHC binding. The presented structure-activity relationships open the door to the rational design of peptide-based vaccines and of nonnatural T-cell receptor antagonists aimed at blocking peptide-specific T-cell responses in MHC-associated autoimmune diseases.

  DOI：

  10.1021/jm981123l

文献信息

• Nonapeptide Analogues Containing (<i>R</i>)-3-Hydroxybutanoate and β-Homoalanine Oligomers:  Synthesis and Binding Affinity to a Class I Major Histocompatibility Complex Protein
  作者：Sorana Poenaru、José R. Lamas、Gerd Folkers、José A. López de Castro、Dieter Seebach、Didier Rognan

  DOI：10.1021/jm981123l

  日期：1999.7.1

  Crystal structures of antigenic peptides bound to class I MHC proteins suggest that chemical modifications of the central part of the bound peptide should not alter binding affinity to the MHC restriction protein but could perturb the T-cell response to the parent epitope. In our effort in designing nonpeptidic high-affinity ligands for class I MHC proteins, oligomers of (R)-3-hydroxybutanoate and(or) beta-homoalanine have been substituted for the central part of a HLA-B27-restricted T-cell epitope of viral origin. The affinity of six modified peptides to the B*2705 allele was determined by an in vitro stabilization assay. Four out of the six designed analogues presented an affinity similar to that of the parent peptide. Two compounds, sharing the same stereochemistry (R,R,S,S) at the four stereogenic centers of the nonpeptidic spacer, bound to B*2705 with a 5-6-fold decreased affinity. Although the chiral spacers do not strongly interact with the protein active site, there are configurations which are not accepted by the MHC binding groove, probably because of improper orientation of some lateral substituents in the bound state and different conformational behavior in the free state, However we demonstrate that beta-amino acids can be incorporated in the sequence of viral T-cell epitopes without impairing MHC binding. The presented structure-activity relationships open the door to the rational design of peptide-based vaccines and of nonnatural T-cell receptor antagonists aimed at blocking peptide-specific T-cell responses in MHC-associated autoimmune diseases.