Part I. Analogs of phosphotyrosine-containing peptides: Synthesis of potential inhibitors of phosphopeptide-SH2 domain interactions. Part II. The rapid screening of a combinatorial library of peptide-encapsulated cadmium sulfide nanoclusters by size-exclusion chromatography.

摘要

Part I. Tyrosine kinases are important regulators of a variety of cellular processes including DNA synthesis and cell proliferation. Therefore, tight regulation of their kinase activity is important in maintaining normal cellular signaling. Phosphorylation/dephosphorylation of proteins plays a major role in their activity. One aspect of this regulation involves the binding of proteins containing phosphotyrosine to the Src homology 2 (SH2) domain of a second protein. Since SH2 domains are known to bind small phosphopeptides, these peptides and their analogs represent a possible mechanism with which to regulate signal-transducing pathways.; We report the synthesis of thiophosphate analogs of phosphoamino acids and incorporation of the nonhydrolyzable synthons into peptides. We also report the synthesis of a novel phosphoramidate analog of phosphotyrosine and attempts to synthesize a peptide containing this derivative. Lastly, attempts were made to study the possible inhibitory role of these analogs on the interactions of pYEEI-containing peptides and the SH2 domain of Lyn kinase.; Part II. The synthesis of monodisperse cadmium sulfide (CdS) nanocrystallites are of interest due to their non-linear optical and quantum confined properties. Quite often nature provides clues to the synthesis of materials through biomineralization or bioremediation processes. Plants and yeast utilize short cysteine-rich matrix peptides (phytochelatins) to synthesize these biogenic nanocrystallites as a method of Cd detoxification.; We have used combinatorial chemistry to develop a spatially addressable peptide library based on the cysteine-rich matrix peptides. These peptides were used to synthesize CdS nanoclusters and their size and monodispersity were examined by size-exclusion chromatography. We applied a materials informatics approach in both the global and positional analysis of the ligand peptides to assess what properties of the peptide are important for the synthesis of a cluster of specific molecular weight. Such insight can be applied in the design of second-generation ligands for the assembly of higher-order nanostructures.