Catch and Release Radiolabeled Peptides: a new technology for radiotracer development

捕获并释放放射性标记肽：放射性示踪剂开发的新技术

• 批准号: 10593475
• 负责人: Matthew Parker
• 金额: $ 24.18万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593475
• 关键词: Amino Acids; Automation; Bacteriophages; Binding; Biological Assay; Biology; Cells; Chemicals; Chemistry; Clinical; Collection; Development; Diagnosis; Diagnostic; Discitis; Dose; Ensure; Escherichia coli; Evaluation; Fluorine; Formulation; Goals; Human; Image; Imaging Device; Infection; Inflammation; Injections; Label; Libraries; Medicine; Methods; Modeling; Molecular; Mus; Myositis; Oncology; Organism; Osteomyelitis; Peptide Synthesis; Peptides; Phage Display; Pharmacology; Play; Positron; Positron-Emission Tomography; Process; Proxy; Radiochemistry; Radiolabeled; Reaction; Research; Role; Sampling; Series; Side; Soft Tissue Infections; Specificity; Staphylococcus aureus; Staphylococcus aureus infection; Sterility; Structure; Techniques; Technology; Testing; Therapeutic; Time; Tracer; Translating; Variant; Wild Type Mouse; antimicrobial peptide; biological systems; clinical translation; cost; density; drug development; drug discovery; expectation; imaging agent; improved; in vitro Assay; infection management; information gathering; molecular imaging; mouse model; new technology; novel; novel strategies; pathogen; pathogenic bacteria; radiochemical; radiotracer; reconstitution; screening; septic; small molecule; spine bone structure; tool

PROJECT SUMMARY Radiolabeled peptides are emerging as a very valuable class of radiotracers that are seated in a unique chemical space, exploiting many of the advantages of small molecules and large biomolecules. To date, they have mostly been used in the oncology field for imaging and treatment. Important to note that peptides are widely sought in drug development for the same reasons. This mass appeal is mostly in part to the high density of chirality and functionality that peptides possess as well as their ease of synthesis which has significantly benefited from automation. In addition, several technologies exist, like one-bead-one-compound libraries and phage display approaches that render discovering biologically-relevant, target-specific peptides quite easy. A new twist on some very old chemistry has paved the way for a new technology in the radiolabeling of peptides that yields high purity, high molar activity tracers in biologically compatible formulation without need for costly reconstitution and purification steps, and can potentially be fully integrated into existing automated peptide synthesis. A technology like this would tremendously benefit the synthesis, evaluation and clinical translation of peptide radiotracers. Beyond this, however, this technology offers new opportunities to integrate positron emission labeled molecules in drug discovery and pharmacology. A robust and automated platform to radiolabel a richly diverse class of molecules could be used to assess collections of molecules in single molecular interactions, in cells and in living biological systems. The goal of this proposal is the development of a new radiolabeling technical platform for peptides and apply it to a group of phage-selected antimicrobial peptides. The study of this group of labeled compounds will be conducted in parallel to assist in the discovery of new biologically-relevant, target-specific peptides, as well as, gaining fundamental understanding of the structure and function relationships of groups of peptides. The information gathered from this project will play in important role in the development of new imaging agents and therapies.

项目摘要 放射标记的肽正在成为一种非常有价值的放射性示踪剂，它们坐在独特的化学物质中 空间，利用小分子和大分子的许多优势。迄今为止，他们大多 被用于肿瘤学领域进行成像和治疗。重要的是要注意，广泛寻求的肽 药物开发的原因相同。这种大规模吸引力主要是在高密度的一部分和 肽所具有的功能以及其易于合成的功能，从而显着受益 自动化。此外，存在几种技术，例如单珠一个化合物库和噬菌体显示器 使发现与生物学相关的，靶标特异性肽的方法非常容易。新的转折 一些非常古老的化学反应为一种新技术铺平了道路，用于肽的放射标记 纯度，高摩尔活性示踪剂在生物学上兼容的配方中，无需昂贵的重建和 纯化步骤，并有可能完全集成到现有的自动化肽合成中。 这样的技术将极大地使肽的合成，评估和临床翻译受益 放射性示例。但是，除此之外，这项技术还提供了整合正电子排放的新机会 药物发现和药理学中的标记分子。一个强大且自动化的平台，可用于Radiolabel丰富 多种类别的分子可用于评估单个分子相互作用中分子的集合，在 细胞和生物生物系统。 该建议的目的是开发一个新的放射性标记技术平台，并应用它 到一组噬菌体选择的抗菌肽。对这组标记化合物的研究将是 并行进行，以帮助发现新的与生物学相关的靶肽以及 了解肽组的结构和功能关系的基本理解。这 从该项目中收集的信息将在新成像代理的开发中发挥重要作用， 疗法。