CATALYZED AMIDE ISOMERIZATION: SYNTHETIC ROTAMASES
催化酰胺异构化:合成旋转异构酶
基本信息
- 批准号:2655017
- 负责人:
- 金额:$ 9.64万
- 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:1997-02-01 至 2002-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION; The goal of this proposal is to disvover mild, selective
catalysts for amide isomerization (AI), culminating in the systematic
development of model rotamase enzymes that catalyze the folding of peptides
through the cis-trans isomerization of proline residues. The PI indicates
that in turn he proposes experiments that address various individual facets
of rotamase catalysis, including metal iion catalysis; catalysis by
desolvation; catalysis by distortion; and autocatalysis and that finally he
integrates these diverse concepts together into a proposal for synthetic
rotamases using the strategy of molecular imprintation, wherein a synthetic
template molecule, or "hapten", is complexed non-covalently with a modified
crosslinking reagent, the template assemblies are then copolymerized with
suitable nomomers to produce highly cros-linked, macroporous polymers and
template molecules are removed to leave beha=ind rigid cavities able to
recognize amides which resemble the template in terms of shape, or more
recognize amides which resemble the template in terms of shape, or more
subtly, hydrogen bond donor or acceptor ability. It is noted that since the
template is designed to closely mimic the transition state for AI
(especially proline isomerization), the polymer would serve as a totally
synthetic rotamase enzyme.
Preliminary data include the first documented cases of metal ion catalyzed
AI, employing substoichiometric amounts of metal under mild conditions;
general acid-catalyzed AI; autocatalysis in model systems; and
miceelle-catalyzed AI, which for the first tiem models the effects of
enzymatic desolvation on rotamase activity. The PI notes that his primary
objective is to understand in detail the various complex factors dictating
rotamase catalysis, to apply his preliminary results to problems in organic
synthesis, and to catalyze the folding of increasingly complex systems
including polypeptides and eventually proteins. He suggests that aside from
the fundamental understanding of rotamase catalysis that this study will
help achieve, practical applications include the development of novel
enantioselective transformaitons.
描述;本提案的目标是驳斥温和的、有选择性的
酰胺异构化(AI)的催化剂,最终在系统
催化肽折叠的模式旋转异构酶的开发
通过脯氨酸残基的顺反异构化。 PI显示
他提出了针对不同方面的实验,
包括金属离子催化;
去溶剂化、畸变催化和自催化,最后,
将这些不同的概念整合在一起,
使用分子印迹的策略,其中合成的
模板分子或“半抗原”与修饰
交联剂,然后将模板组装体与交联剂共聚,
制备高度交联的大孔聚合物的合适的单体,
除去模板分子以留下Behind刚性空腔,
识别在形状方面类似于模板的酰胺,或更多
识别在形状方面类似于模板的酰胺,或更多
微妙地,氢键供体或受体能力。 据指出,由于
模板被设计成紧密地模仿AI的过渡状态
(特别是脯氨酸异构化),聚合物将作为一个完全的
合成旋转异构酶。
初步数据包括首次记录的金属离子催化的
Al,在温和条件下使用亚化学计量量的金属;
一般酸催化AI;模型系统中的自催化;以及
胶束催化的AI,这是第一次模拟的影响,
酶促去溶剂化对旋转异构酶活性的影响。 PI指出,他的主要
目标是详细了解决定
旋转异构酶催化,将他的初步结果应用于有机问题
合成,并催化日益复杂的系统的折叠
包括多肽和最终的蛋白质。 他认为,除了
这项研究将有助于对旋转异构酶催化作用的基本理解,
帮助实现,实际应用包括开发新的
对映选择性转化
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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THOMAS C. LECTKA其他文献
THOMAS C. LECTKA的其他文献
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{{ truncateString('THOMAS C. LECTKA', 18)}}的其他基金
Contaminant-FreeKetene Synthesis for Asymmetric Catalysi
用于不对称催化的无污染乙烯酮合成
- 批准号:
6620589 - 财政年份:2002
- 资助金额:
$ 9.64万 - 项目类别:
Contaminant-FreeKetene Synthesis for Asymmetric Catalysi
用于不对称催化的无污染乙烯酮合成
- 批准号:
7019573 - 财政年份:2002
- 资助金额:
$ 9.64万 - 项目类别:
Contaminant-FreeKetene Synthesis for Asymmetric Catalysi
用于不对称催化的无污染乙烯酮合成
- 批准号:
6837148 - 财政年份:2002
- 资助金额:
$ 9.64万 - 项目类别:
Contaminant-FreeKetene Synthesis for Asymmetric Catalysi
用于不对称催化的无污染乙烯酮合成
- 批准号:
7193322 - 财政年份:2002
- 资助金额:
$ 9.64万 - 项目类别:
Contaminant-FreeKetene Synthesis for Asymmetric Catalysi
用于不对称催化的无污染乙烯酮合成
- 批准号:
6694069 - 财政年份:2002
- 资助金额:
$ 9.64万 - 项目类别:
Contaminant-FreeKetene Synthesis for Asymmetric Catalysi
用于不对称催化的无污染乙烯酮合成
- 批准号:
6419241 - 财政年份:2002
- 资助金额:
$ 9.64万 - 项目类别:
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