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Collaborative Research: Nucleobase-Modified Peptide Nucleic Acid (PNA) for Sequence Selective Triple-Helical Recognition of Non-Coding Ribonucleic Acid (RNA)

合作研究：核碱基修饰肽核酸 (PNA) 用于非编码核糖核酸 (RNA) 的序列选择性三螺旋识别

基本信息

批准号：
1708761
负责人：
Eriks Rozners
金额：
$ 50.19万
依托单位：
SUNY at Binghamton
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1708761&HistoricalAwards=false
关键词：
Collaborative Research Nucleobase Modified Peptide

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding a collaborative effort between Professors Eriks Rozners (Binghamton University) and James A. MacKay (Elizabethtown College). The research develops new methods for molecular recognition of biologically-significant, non-coding ribonucleic acid (RNA). The majority of cellular RNA consists of non-coding RNAs that play important roles in regulating gene expression even though these processes are not fully understood. Selective recognition, imaging, and functional regulation of such RNAs are useful for fundamental studies and practical applications in biotechnology. The project expands interdisciplinary, collaborative research across traditional institutional boundaries. The project establishes a bridge for Elizabethtown College (a primarily undergraduate institution) students to transition from undergraduate studies to advanced graduate studies at a research university. Undergraduate students, especially women, minorities and first generation college students, participate in the project. The project also contributes to improving STEM education. The development of sequence selective RNA binders is important for understanding the biochemistry of non-coding RNAs. Such binders may impact fundamental RNA biology and practical applications in biotechnology and synthetic biology. This collaborative study is developing new peptide nucleic acid (PNA) nucleobases that enable recognition of the entire Hoogsteen face of Watson-Crick and non-canonical base pairs of double-stranded RNA. The properties of the novel nucleobases are optimized using synthetic organic chemistry to enable recognition of any sequence of double-stranded RNA. This approach may solve a long-standing problem in molecular recognition of RNA and enables a variety of applications. Examples of such applications are: imaging and functional control of regulatory RNA, designer riboswitches for synthetic biology, and inhibition of biologically-important RNA for fundamental studies.

有了这个奖项，化学系的生命过程化学项目正在资助Eriks Rozners教授（宾厄姆顿大学）和James A.麦凯（伊丽莎白敦学院）。该研究为具有生物学意义的非编码核糖核酸（RNA）的分子识别开发了新方法。大多数细胞RNA由非编码RNA组成，这些非编码RNA在调节基因表达中发挥重要作用，尽管这些过程尚未完全理解。这些RNA的选择性识别、成像和功能调节对于生物技术的基础研究和实际应用是有用的。该项目跨越传统的机构界限，扩大了跨学科的合作研究。该项目为伊丽莎白敦学院（主要是本科院校）的学生从本科学习过渡到研究型大学的高级研究生学习搭建了一座桥梁。本科生，特别是妇女、少数民族和第一代大学生参加了该项目。该项目还有助于改善STEM教育。序列选择性RNA结合剂的开发对于理解非编码RNA的生物化学是重要的。这种粘合剂可能会影响基本的RNA生物学和生物技术和合成生物学的实际应用。这项合作研究正在开发新的肽核酸（PNA）核碱基，能够识别沃森-克里克的整个Hoogsteen面和双链RNA的非规范碱基对。使用合成有机化学优化新型核碱基的性质，以使其能够识别任何双链RNA序列。这种方法可以解决RNA分子识别中的一个长期存在的问题，并使各种应用成为可能。这些应用的例子有：调控RNA的成像和功能控制，合成生物学的设计核糖开关，以及基础研究中生物学重要RNA的抑制。