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
基本信息
- 批准号:10593475
- 负责人:
- 金额:$ 24.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:Amino AcidsAutomationBacteriophagesBindingBiological AssayBiologyCellsChemicalsChemistryClinicalCollectionDevelopmentDiagnosisDiagnosticDiscitisDoseEnsureEscherichia coliEvaluationFluorineFormulationGoalsHumanImageImaging DeviceInfectionInflammationInjectionsLabelLibrariesMedicineMethodsModelingMolecularMusMyositisOncologyOrganismOsteomyelitisPeptide SynthesisPeptidesPhage DisplayPharmacologyPlayPositronPositron-Emission TomographyProcessProxyRadiochemistryRadiolabeledReactionResearchRoleSamplingSeriesSideSoft Tissue InfectionsSpecificityStaphylococcus aureusStaphylococcus aureus infectionSterilityStructureTechniquesTechnologyTestingTherapeuticTimeTracerTranslatingVariantWild Type Mouseantimicrobial peptidebiological systemsclinical translationcostdensitydrug developmentdrug discoveryexpectationimaging agentimprovedin vitro Assayinfection managementinformation gatheringmolecular imagingmouse modelnew technologynovelnovel strategiespathogenpathogenic bacteriaradiochemicalradiotracerreconstitutionscreeningsepticsmall moleculespine bone structuretool
项目摘要
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
放射性标记肽是一类非常有价值的放射性示踪剂,它们位于一种独特的化学物质中,
空间,利用小分子和大生物分子的许多优点。到目前为止,他们大多
在肿瘤学领域用于成像和治疗。重要的是要注意,肽是广泛寻求的,
药物开发出于同样的原因。这种大规模的吸引力主要部分是由于手性的高密度,
肽具有的功能性以及它们的易于合成,这显著受益于
自动化.此外,存在几种技术,如一珠一化合物文库和噬菌体展示
使发现生物相关的、靶向特异性肽变得非常容易的方法。的新转折
一些非常古老的化学方法为放射性标记肽的新技术铺平了道路,
- 在生物相容的制剂中的纯度、高摩尔活性示踪剂,而不需要昂贵的重构,
该方法可以用于纯化步骤,并且可以潜在地完全整合到现有的自动化肽合成中。
这一技术将极大地有利于肽的合成、评价和临床翻译
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,用于放射性标记丰富的
不同种类的分子可用于评估单个分子相互作用中的分子集合,
细胞和活的生物系统中。
本项目的目标是建立一种新的多肽放射性标记技术平台并应用于临床
一组噬菌体选择性抗菌肽。对这组标记化合物的研究将是
平行进行,以帮助发现新的生物学相关的靶特异性肽,以及,
获得对肽组的结构和功能关系的基本理解。的
本项目所收集的信息将在新显像剂的开发中发挥重要作用,
治疗
项目成果
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