Spontaneous Membrane Translocating Peptides
自发膜转位肽
基本信息
- 批准号:9536104
- 负责人:
- 金额:$ 31.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-15 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:ArginineBehaviorBindingBiologicalBiological AssayBypassCationsCellsChargeChemicalsCommunitiesDrug DesignElectrostaticsEngineeringEnsureFamilyFutureGoalsHydrocarbonsHydrophobicityLearningLeucineLipid BilayersLipidsLuciferasesMeasurementMeasuresMembraneModificationMolecular ChaperonesMovementNeutron DiffractionOligonucleotidesPeptide Nucleic AcidsPeptidesPopulationPropertyRNA SplicingRoleSmall Interfering RNASolubilityStructureStructure-Activity RelationshipSystemTestingVariantVesicleWorkX ray diffraction analysisanalogbasebiophysical propertiesdesigninorganic phosphateknock-downnovelpenetratinphysical propertyprotein expressionresponsesolutesynthetic nucleic acid
项目摘要
Summary
The hydrocarbon core of a bilayer is normally a strict barrier to the passage of polar or charged
solutes. We have discovered a novel class of cationic peptides that efficiently cross this barrier
without causing bilayer permeabilization. These peptides are fundamentally different from other
classes of membrane active peptides, and may hold the key to understanding how to bypass
the barrier of the hydrocarbon core on demand. Yet, the determinants of this behavior are
currently unknown. Here we will explore the physical chemical basis of peptide translocation by
comprehensively examining rationally designed sequence variants of a known translocating
peptide. The overarching hypothesis of this proposal is that translocation occurs only if the
peptides have a specific translocation-enabling sequence motif and optimal hydrophobicity.
Here we will test the hypothesis that translocation of peptides across bilayers requires optimal
hydrophobicity that ensures a low steady state population in a membrane, and a specific
sequence motif consisting of two arginines spaced by two hydrophobic residues, embedded in
a hydrophobic sequence. We will determine the importance of these translocation-permissive
properties by varying them independently by rational sequence modification and assessing the
effect on (1) translocation across bilayers, (2) binding to bilayers, and (3) the structural response
of the bilayer to the peptides.
摘要
双层的碳氢化合物核心通常是极性或带电通过的严格屏障。
溶质。我们已经发现了一类新型的阳离子多肽,它们可以有效地跨越这一障碍
而不会引起双层渗透。这些多肽与其他多肽有根本的不同
膜活性多肽的种类,可能是了解如何绕过的关键
碳氢化合物核心的需求障碍。然而,这种行为的决定因素是
目前尚不清楚。在这里,我们将探索多肽转位的物理化学基础,通过
全面考察已知易位的合理设计的序列变体
多肽。这一提议的首要假设是,只有当
多肽具有特定的易位使能序列基序和最佳的疏水性。
在这里,我们将检验这样一个假设,即多肽在双层之间的转移需要最佳
疏水性,确保膜中的低稳定状态种群,以及特定的
序列基序由两个精氨酸和两个疏水残基组成,嵌入在
一种疏水序列。我们将确定这些移位的重要性-允许
属性,通过合理的序列修改独立地改变它们,并评估
对(1)跨双层转运、(2)与双层结合和(3)结构响应的影响
多肽的双层结构。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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WILLIAM C WIMLEY其他文献
WILLIAM C WIMLEY的其他文献
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{{ truncateString('WILLIAM C WIMLEY', 18)}}的其他基金
Structure and Function of Direct Delivery Peptides
直接递送肽的结构和功能
- 批准号:
10717736 - 财政年份:2023
- 资助金额:
$ 31.62万 - 项目类别:
Mechanism of Resistance Avoidance in Synthetically Evolved Antibacterial Peptides
合成进化抗菌肽避免耐药性的机制
- 批准号:
10412134 - 财政年份:2021
- 资助金额:
$ 31.62万 - 项目类别:
Mechanism of Resistance Avoidance in Synthetically Evolved Antibacterial Peptides
合成进化抗菌肽避免耐药性的机制
- 批准号:
10308818 - 财政年份:2021
- 资助金额:
$ 31.62万 - 项目类别:
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