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.

项目概要 放射性标记肽正在成为一类非常有价值的放射性示踪剂，它们位于独特的化学物质中 太空，利用小分子和大生物分子的许多优点。迄今为止，他们大多已 已用于肿瘤学领域的成像和治疗。值得注意的是，肽在以下领域被广泛寻求： 出于同样的原因进行药物开发。这种大众吸引力主要部分归因于高密度的手性和 肽所具有的功能性以及合成的简易性，这显着受益于 自动化。此外，还存在多种技术，例如一珠一化合物库和噬菌体展示 这些方法使得发现生物学相关的、靶标特异性的肽变得相当容易。新的转折 一些非常古老的化学方法为肽放射性标记新技术铺平了道路，该技术可产生高产率 生物相容性制剂中的纯度、高摩尔活性示踪剂，无需昂贵的重构和 纯化步骤，并且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有利于肽的合成、评估和临床转化 放射性示踪剂。然而除此之外，这项技术还提供了整合正电子发射的新机会 药物发现和药理学中的标记分子。一个强大的自动化平台，可以丰富地进行放射性标记 不同类别的分子可用于评估单分子相互作用中的分子集合，例如 细胞和活的生物系统中。 该提案的目标是开发一种新的肽放射性标记技术平台并应用 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，以协助发现新的生物学相关的、针对特定目标的肽，以及， 获得对肽基团的结构和功能关系的基本了解。这 从该项目收集的信息将在新显像剂的开发和 疗法。