Synthetic selective and differential receptors for the recognition of bioanalytes

This dissertation consists of five chapters. The first chapter provides an in-depth background of supramolecular chemistry and differential recognition. The first chapter also elaborates upon the necessary requirements for successful application of chemosensor assays and arrays. Additionally, sensing mechanisms and chemometric pattern recognition is described for clarification of the research conducted in chapters 2- 5. Chapter 2 discusses the synthesis and employment of a metalated receptor for the selective recognition of the tripeptide His-Lys-Lys. A receptor was synthesized with two peptide arms emanating outward from a metal ligand core using both solution and solid phase chemistry. UV/Vis titrations were used to determine binding constants for various amino acids and tripeptides to the synthetic receptor:Cu(II) complex. The receptor:Cu(II) complex was found to be selective for His-Lys-Lys over other tripeptides, amino acids, and protected amino acids. viii Chapter 3 describes the synthesis and application of a fluorescent chemosensor for the recognition of unfractionated and low-molecular weight heparin. Heparin is a commonly used clinical anticoagulant for surgical situations and post-operative outpatient care. Due to the high selectivity of the receptor for heparin, studies in crude serum were attempted. It was found that the receptor was selective for heparin in serum. Therefore, fluorescent calibration charts were prepared for quantifying heparin at clinical concentrations using the synthetic receptor. This research is one of very few to be published regarding the creation of synthetic receptors with sufficient selectivity for activity in biological media. Chapter 4 describes the combinatorial synthesis of two resin-bound receptor libraries for use in differential recognition studies. The two libraries, in conjunction with an indicator-uptake assay, were used for the detection and discrimination of three proteins and two glycoproteins as well as four tripeptides and three tripeptide mixtures using pattern recognition protocols. Chapter 5 discusses the preparation and screening of a metalated receptor library. A colorimetric mimic of a tachykinin hormone, α-neurokinin, was created and used to screen the receptor library. Seven selective receptors were identified and subsequently sequenced to determine their molecular architecture. The receptors were resynthesized and employed in solution phase binding studies with α-neurokinin.