Synthesis, cellular studies, and computational analysis of porphyrin and BODIPY conjugates with affinity for epidermal growth factor receptor

Abstract

Chapter 1 is a description of the basic fundamental concepts of porphyrins and BODIPYs, (including synthetic methodologies), a general mechanism of the processes of EGFR, and computational concepts that are elaborated upon in future chapters. Chapter 2 is a discussion solely on the porphyrins that were synthesized to be used as fluorophores for EGFR-targeted conjugates, both peptidic and non-peptidic. The porphyrins were primarily synthesized via the Lindsey method as well as by O-alkylation of tetrahydroxy porphyrins. Synthesis of PEG linkages are discussed as well through three methodologies. Chapter 3 is a presentation of the synthesis, characterization, cellular studies, and computational analysis of porphyrin-tyrphostin conjugates that will be used as potential in vivo imaging agents for CRC. Two tyrphostin molecules that have affinity for EGFR, the BMNs and quinazolines, were synthesized and conjugated to PEG and or a porphyrin-PEG. Chapter 4 is a report of the development of porphyrin-peptide conjugates using two peptides, EGFR L1 (a six amino acid peptide) and EGFR L2 (a twelve amino acid peptide). The peptides differ in charge, length, and hydrophobic character. Porphyrin-peptide conjugates were synthesized via SPS or SNS methods using typical peptide coupling agents. Cellular studies are also reported. Chapter 5 is a presentation of the synthesis and characterization of novel BODIPY-peptidomimetic conjugates. The peptidomimetic was designed computationally. Two methods of conjugation are described: SNS with a tert-butyl ester protected peptidomimetic, and SPS. This work was done in collaboration with Professor S. Jois at University of Louisiana-Monroe.