Synthetic Chemistry Core

该核心的总体目标是为NCDDG的所有三个项目提供化学支持，以便淋巴瘤靶向药物的临床候选药物将在本研究的第五年结束时准备好进行临床试验。最先进的组合文库方法将用于发现细胞表面结合肽，这将证明在治疗和治愈难治性人类b细胞恶性肿瘤中有用。该核心的主要目标是开发使用肽和拟肽化合物开发癌症靶向治疗所需的所有化学物质。该核心提供的具体服务包括：单头单化合物组合文库的设计与合成，全细胞筛选分离的阳性化合物珠的微测序与解码，设计

The overall goal of this core is to provide chemical support for all the three programs of this NCDDG, so that clinical candidate for lymphoma targeting agents will be ready for clinical testing by the end of the fifth year of this proposed research. State-of-the-art combinatorial library methods will be used to discover cell surface binding peptides that will prove useful in the treatment and cure of refractory human B-cell malignancies. The main objective of this core is to develop all the chemistries needed for the development of targeted-therapy in cancers using peptide and peptidomimetic compounds. Specific services provided by this core are as follows: design and synthesis of one-bead one-compound combinatorial libraries, microsequencing and decoding of positive compound-beads isolated through whole-cell screening, design and synthesis of chemical microarrays for cell adhesion profiling, design and synthesis of various ligand-conjugates (fluorescent, biotinylated, photo- and chemo-affinity label, and DOTA-labled ligands, toxin-ligand) to be used by all 3 programs for either in vitro or in vivo studies. For the DOTA-labeled ligands, monovalent, bivalent, and oligovalent forms will be prepared for determination of the optimal form with favorable pharmacokinetic parameters.