Source: Dissertation Abstracts International, Volume: 78-01(E), Section: B.

Adviser: David A. Spiegel.

Chapter 1: An introduction to solid-phase combinatorial chemistry and One-Bead-OneCompound (OBOC) screening. A brief review of the commonly used oliogomeric scaffolds used in combinatorial chemistry and the technical limitations of this screening process.

Chapter 2: The synthesis of modular oligomeric scaffolds, such as peptides and peptoids, combined with the one-bead-one compound (OBOC) screening provide a rapid technology for target ligand identification. Despite the advantages of this technology there is a need to develop new chemical scaffolds to improve ligand diversity. Herein we introduce a novel scaffold called peptidines; this oligomer utilizes an amidine functional group as the key repeating linkage. We demonstrate an efficient and modular method to produce these compounds in solution and solid phases and investigate peptidines' structural properties.

Chapter 3: OBOC screening platforms provide a method to rapidly screen collections of small molecules to bind biological targets (antibodies, proteins, cells). This process, however, suffers from high-false positive rates, the requirement for orthogonal tagging of beads with Mass-Spec (MS) decodable ligands, and, ultimately, the majority of information from a screen is discarded. We developed a new platform for OBOC screening that addressed these limitations by using an alternative solid support called pChips, which are RFID-encoded silicon microtransponders as opposed to polymer resin. We developed a polyethylene glycol methancrylate (PEGMA) coating procedure that was compatible with Fmoc solid-phase peptide synthesis (SPPS) and carry out on-chip ID-tracked peptide synthesis and on-chip anti-hemagglutinin (HA) antibody screening. We believe that utilizing pChips and their universal ID and decoding systems will improve solid-phase screening.

Chapter 4: To Further development in OBOC screening platforms was conducted by improving upon the pChip project by producing our in-house visual barcode encoded chips called sChips. These chips were designed such that they could be produced at a cheapter cost, higher quanities, and high-throughput evaluated for biological binding using a microscope enabling larger chip collections to be used during screening.