Core--Synthetic Chemistry

这个核心的总体目标是为NCDDG的所有三个项目提供化学支持，以便在这项拟议研究的第五年结束时，淋巴瘤靶向药物的临床候选药物将准备好进行临床测试。最先进的组合文库方法将被用来发现细胞表面结合多肽，这将被证明在治疗和治疗人类难治性B细胞恶性肿瘤方面有用。这一核心的主要目标是开发利用多肽和模拟多肽化合物进行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：一珠一化合物组合文库的设计和合成，全细胞筛选分离的阳性化合物珠的微测序和解码，设计 和合成用于细胞黏附分析的化学微阵列，设计和合成各种配体结合物(荧光、生物素化、光和化学亲和标记，以及DOTA标记的配体、毒素配体)，供所有3个项目用于体外或体内研究。对于DOTA标记的配体，将制备单价、二价和寡价形式，以确定具有良好药代动力学参数的最佳形式。

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.