MIMICS OF HELIX TURN HELIX PEPTIDES
螺旋转角螺旋肽的模拟物
基本信息
- 批准号:6180628
- 负责人:
- 金额:$ 4.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-05-01 至 2000-08-09
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: The goal of this project is to mimic the helix-turn-helix
(HTH) motif of the POU Oct-1 homeodomain and the 434 Cro repressor by
constraining the native conformation of this small portion of the protein.
The helix-turn-helix motif is found in several DNA-binding proteins that
have known 3-dimensional structures. Such chimeric molecules can serve a
two-fold health-related purpose. First, the design and biochemical
evaluation of the chimeric molecules will explore fundamental aspects of
protein folding and protein-DNA interactions. Second, each of the mimics
described could serve as biochemical probes of developmental processes. POU
homeodomains are transcription factors for human growth hormone, histones,
snRNAs, immunoglobulin, herpes simplex virus and other medically important
genes. The PI proposes to constrain the conformation of peptides
corresponding to the HTH motif via covalent bonds between buried hydrophobic
side-chains. Two approaches to this unusual type of side-chain linkage will
be taken: 1) aryl linkage and 2) alkyl linkage. The templates are designed
to stabilize the conformation of the flexible turn. The designs feature
stable organic side-chains which will favor protein folding by burial of the
additional hydrophobic moiety. Each template will be synthesized
stereospecifically from amino acid starting materials and incorporated by
solid-phase synthesis into a peptide corresponding to the sequence of the
structurally well-characterized Cro repressor and POU Oct-1 homeodomain.
Peptide engineering of the alpha-helices will introduce salt bridges and
residues with high helix propensities to improve the helicity of attached
peptides. A helix-to-helix crosslink will be introduced to improve the
tertiary structure stability. The HTH mimics will be characterized
chemically (HPLC, MS, NMR), structurally (CD, NMR and/or x-ray
crystallography) and functionally (DNA-binding affinity) to ascertain the
success of the mimics.
描述:这个项目的目标是模拟螺旋-螺旋-螺旋
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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FELICIA A ETZKORN其他文献
FELICIA A ETZKORN的其他文献
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{{ truncateString('FELICIA A ETZKORN', 18)}}的其他基金
THE ROLE OF PIN1 IN MITOSIS WITH DESIGNED INHIBITORS
PIN1 在有丝分裂中与设计抑制剂的作用
- 批准号:
6335974 - 财政年份:2000
- 资助金额:
$ 4.37万 - 项目类别:
THE ROLE OF PIN1 IN MITOSIS WITH DESIGNED INHIBITORS
PIN1 在有丝分裂中与设计抑制剂的作用
- 批准号:
6387319 - 财政年份:2000
- 资助金额:
$ 4.37万 - 项目类别:
THE ROLE OF PIN1 IN MITOSIS WITH DESIGNED INHIBITORS
PIN1 在有丝分裂中与设计抑制剂的作用
- 批准号:
6526115 - 财政年份:2000
- 资助金额:
$ 4.37万 - 项目类别:
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