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首页> 外文学位 >Design, synthesis, and characterization of anti-estrogenic and anti-breast cancer alpha-fetoprotein-derived peptides.
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Design, synthesis, and characterization of anti-estrogenic and anti-breast cancer alpha-fetoprotein-derived peptides.

机译：抗雌激素和抗乳腺癌甲胎蛋白衍生肽的设计，合成和表征。

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摘要

The null hypothesis of this thesis is that the native primary and secondary structures of existing peptide AFP447–480 are necessary for the antiestrotrophic and anti-oncotic activities associated with the peptide. This hypothesis was tested by completing the following three specific aims: The first specific aim was to determine which structural features of AFP447–480 contribute to its aggregation and loss of activity. The second specific aim was to design, produce, and characterize analogs of AFP447–480 with the goal of enhancing structural stability and preventing the loss of biological activity that occurs during storage. The third specific aim was to determine whether smaller segments of this 34-mer peptide retain biological activity with the goal of identifying the minimal active sequence.; Circular dichroism spectroscopy, gel-filtration chromatography, mass spectrometry, and amino acid analysis were used for physical characterization of the synthetic peptides.; A number of 34-mer peptide analogs were designed to prevent possible disulfide bond formation and beta-sheet formation and were synthesized in attempt to generate an agent that would be stable during storage. These analogs included AFP447–480 (C455A, C468A), AFP447–480 (C455G, C468G), AFP447–480 (C455S, C468S), AFP 447–480 (C455D, C468D), and AFP447–480 (C455P, I463P, C468P).; Several shorter peptides, including an 8-mer called AFP472–479 (amino acids 472–479, peptide sequence EMTPVNPG) retained activity, whereas peptides shorter than eight amino acid residues were inactive.; Physical characterization of octapeptide AFP472–479 indicated that the peptide aggregated during storage to form inactive species.; These data show that octapeptide EMTOVNOG and cyclo-(EMTOVNOGQ), which have approximately 1/3 the size of the original 34-mer peptide, are superior to the parent 34-mer peptide AFP447–480 with respect to structural stability, biological activity, and shelf life. These peptides, or peptidomimetics designed therefrom, may become novel agents for the treatment or even prevention of breast cancer. (Abstract shortened by UMI.)
机译：本论文的无效假设是现有肽AFP 447–480 的天然一级和二级结构对于与该肽相关的抗营养和抗肿瘤活性是必需的。通过完成以下三个特定目标来检验该假设：第一个特定目标是确定AFP 447-480 的哪些结构特征有助于其聚集和活性丧失。第二个具体目的是设计，生产和表征AFP 447-480 的类似物，目的是增强结构稳定性并防止在储存过程中发生生物活性丧失。第三个具体目的是确定该34聚体肽的较小片段是否保留生物活性，以鉴定最小活性序列。圆二色谱，凝胶过滤色谱，质谱和氨基酸分析用于合成肽的物理表征。设计了许多34-mer肽类似物，以防止可能形成二硫键和形成β-折叠，并进行合成以试图生成在储存过程中稳定的试剂。这些类似物包括AFP 447–480（C455A，C468A），AFP 447–480（C455G，C468G），AFP 447–480（C455S，C468S）< / sub>，AFP 447–480（C455D，C468D）和AFP 447–480（C455P，I463P，C468P）。几种较短的肽，包括称为AFP 472-479 的8-聚体（氨基酸472-479，肽序列EMTPVNPG）保留了活性，而短于8个氨基酸残基的肽则没有活性。八肽AFP 472-479 的物理特征表明，该肽在储存过程中会聚集形成惰性物质。这些数据表明，八肽EMTOVNOG和环-（EMTOVNOGQ）的大小约为原始34-mer肽的1/3，优于其亲本34-mer肽AFP 447-480 。关于结构稳定性，生物活性和保质期。这些肽或由其设计的肽模拟物可以成为治疗或什至预防乳腺癌的新型药物。 （摘要由UMI缩短。）

著录项

  • 作者

    Mesfin, Fassil Brian.;

  • 作者单位

    Albany Medical College of Union University.;

  • 授予单位 Albany Medical College of Union University.;
  • 学科 Chemistry Biochemistry.; Biology Molecular.; Biophysics Medical.; Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 183 p.
  • 总页数 183
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;分子遗传学;生物物理学;肿瘤学;
  • 关键词

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