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

项目总结 放射性标记多肽正在成为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势。到目前为止，他们已经基本上 已用于肿瘤学领域的成像和治疗。重要的是要注意，多肽在 出于同样的原因进行药物开发。这种大众吸引力主要是由于手性和手性的高密度 多肽具有的功能以及它们的合成简便性，这一点大大受益于 自动化。此外，还存在几种技术，如一珠一复合库和噬菌体展示 使发现与生物相关的、靶标特异性多肽变得非常容易的方法。新的转折发生在 一些非常古老的化学已经为一种新的多肽放射性标记技术铺平了道路，这种多肽产生的高产量 生物相容配方中的纯度、高摩尔活度示踪剂，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多肽合成。 这样的技术将极大地促进多肽的合成、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，用于标记丰富的 不同类别的分子可以用来评估单分子相互作用中的分子集合 细胞和活的生物系统中。 这项提案的目标是开发一种新的多肽放射性标记技术平台并将其应用于 一组噬菌体选择的抗菌肽。对这组标记化合物的研究将是 同时进行，以协助发现新的生物相关、靶标特异的多肽，以及， 对多肽的结构和功能关系有了基本的了解。这个 从该项目收集的信息将在开发新的显像剂和 治疗。

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.