Structure-Function Relationships in Lung Surfactants

肺表面活性剂的结构-功能关系

基本信息

批准号：
7330335
负责人：
Joanna R Long
金额：
$ 27.23万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-01-07 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7330335
关键词：
Address Adopted Adult Respiratory Distress Syndrome Air Alveolus Amino Acid Sequence Amino Acids Animals Anisotropy Behavior Binding Biological Assay Calorimetry Chemicals Clinical Clinical Treatment Clinical Trials Complex Condition Dependence Depth Deuterium Development Differential Scanning Calorimetry Disease Drug Formulations Environment Failure Fluorescence Resonance Energy Transfer Goals Homologous Gene Individual Label Laboratories Length Lipid Bilayers Lipids Location Lung Lung diseases Measures Meconium Aspiration Melanocytic nevus Membrane Membrane Lipids Membrane Proteins Modeling Mole the mammal Molecular Monitor N-terminal Nature Newborn Respiratory Distress Syndrome Palmitic Acids Parents Peptide Sequence Determination Peptides Phase Phospholipids Phosphorous Play Positioning Attribute Premature Infant Preparation Principal Investigator Property Protein Family Proteins Publishing Pulmonary Surfactant-Associated Protein B Pulmonary Surfactant-Associated Proteins Pulmonary Surfactants Relaxation Replacement Therapy Research Resolution Role Sampling Saposins Scheme Severe Acute Respiratory Syndrome Solid Spectroscopy, Fourier Transform Infrared Structural Models Structure Structure-Activity Relationship Surface Properties Surface Tension System Techniques Therapeutic Titrations Vertebral column Water analog base cost design insight molecular modeling monolayer novel peptide analog physical property programs protein structure protein structure function research study solid state success surfactant

项目摘要

DESCRIPTION (provided by applicant): Proteins play critical roles in imparting the unique physical properties in mammalian lung surfactant. Failure to express functional surfactant protein B, SP-B, is lethal, and application of exogenous lung surfactant has proved beneficial in treating some respiratory distress syndromes. However, success or failure of various lung surfactant preparations in treating specific individuals is unpredictable, and a solid understanding of the molecular basis for the role of SP-B in lung surfactant is lacking. Understanding the complex interactions between SP-B and the lipids present in lung surfactant could direct the formulation of clinical surfactant preparations for specific diseases including adult respiratory distress syndrome (ARDS), severe acute respiratory syndrome (SARS), respiratory distress syndrome (RDS) in premature infants, and meconium aspiration. Determining the structure and mechanisms of action for smaller peptide analogs of SP-B would aid in the development of low-cost, synthetic replacement therapies which could replace animal-derived formulations. We propose to study the function of SP-B under physiologically relevant conditions and to determine whether peptide analogs of the N- and C- terminus of SP-B can adopt stable complexes with lipids which mimic the actions of the parent protein. Studying the structure, orientation, and locations of these peptides in bilayer membranes will aid in determining under what conditions they can serve as replacements for the full protein. We will be using novel, sensitive solid state NMR experiments which allow us to determine at atomic resolution these parameters at low concentrations in complex lipid environments.

描述（由申请人提供）：蛋白质在赋予哺乳动物肺表面活性剂中独特的物理特性方面起关键作用。未能表达功能性表面活性剂B，Sp-B是致命的，外源肺表面活性剂的应用已证明有益于治疗某些呼吸遇险综合症。但是，各种肺表面活性剂制剂在治疗特定个体中的成功或失败是不可预测的，并且缺乏对SP-B在肺表面活性剂中作用的分子基础的可靠理解。了解SP-B与肺表面活性剂中存在的脂质之间的复杂相互作用可以指导针对特定疾病的临床表面活性剂制剂制剂，包括成人呼吸窘迫综合征（ARDS），严重的急性呼吸综合征（SARS），早产儿和Meconium吸入中的急性急性呼吸综合征（SARS），呼吸窘迫综合征（RDS）。确定SP-B较小肽类似物的作用的结构和机制将有助于发展低成本的合成替代疗法，这些疗法可以取代动物衍生的配方。我们建议研究在生理相关条件下SP-B的功能，并确定SP-B的N-和C末端的肽类似物是否可以采用模仿父蛋白作用的脂质的稳定复合物。研究这些肽在双层膜中的结构，方向和位置将有助于确定它们在哪种条件下可以作为全蛋白质的替代。我们将使用新型的，敏感的固态NMR实验，使我们能够在原子分辨率下确定这些参数在复杂的脂质环境中低浓度。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Optimizing ssNMR experiments for dilute proteins in heterogeneous mixtures at high magnetic fields.

优化高磁场下异质混合物中稀释蛋白质的 ssNMR 实验。

DOI：
10.1002/mrc.2146
发表时间：
2007
期刊：
Magnetic resonance in chemistry : MRC
影响因子：
0
作者：
McNeill,SethA;Gor'kov,PeterL;Struppe,Jochem;Brey,WilliamW;Long,JoannaR
通讯作者：
Long,JoannaR

Incorporation of isotopically enriched amino acids.

掺入富含同位素的氨基酸。

DOI：
10.1002/0471140864.ps2603s47
发表时间：
2007
期刊：
Current protocols in protein science
影响因子：
0
作者：
Samuel-Landtiser,Mini;Zachariah,Cherian;Williams,ChrisR;Edison,ArthurS;Long,JoannaR
通讯作者：
Long,JoannaR

Partitioning, dynamics, and orientation of lung surfactant peptide KL(4) in phospholipid bilayers.

DOI：
10.1016/j.bbamem.2009.08.020
发表时间：
2010-02
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
影响因子：
3.4
作者：
Long, Joanna R.;Mills, Frank D.;Ganesh, Omjoy K.;Antharam, Vijay C.;Farver, R. Suzanne
通讯作者：
Farver, R. Suzanne

Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation.

DOI：
10.1016/j.bbamem.2008.07.013
发表时间：
2008-11
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
影响因子：
3.4
作者：
Antharam, Vijay C.;Farver, R. Suzanne;Kuznetsova, Anna;Sippel, Katherine H.;Mills, Frank D.;Elliott, Douglas W.;Sternin, Edward;Long, Joanna R.
通讯作者：
Long, Joanna R.