Core--Synthetic Chemistry

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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.