Demonstrating the versatility of the iDNA scaffold: New synthetic strategies and applications

Open Access
Levine, Lauren Aimee
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
August 03, 2009
Committee Members:
  • Mary Elizabeth Williams, Dissertation Advisor
  • Mary Elizabeth Williams, Committee Chair
  • Philip C. Bevilacqua, Committee Member
  • Scott A Showalter, Committee Member
  • John H Golbeck, Committee Member
  • artifical peptides
  • metal-binding
Biological macromolecules including DNA and enzymes have long been the inspiration for the design and construction of synthetic molecular assemblies. Biomolecules have the inherent ability to use molecular recognition to self-assemble functional architectures that are capable of complex catalytic reactions, photochemistry,and storage of information. A major aim of these studies is to develop novel inorganic supramolecular structures that have tunable magnetic, electronic, chemical and physical properties beyond naturally occurring systems. Chapter 2 describes initial studies of the biological interactions between 12mer dsDNA and solid phase synthesized pyridyl tetrapeptides that have been reacted with [Pt(tpy)]2+ to create metallated single-stranded structures. These interactions were probed using ITC, UV and CD thermal denaturation experiments and show that the KB for the metallated peptide represents an affinity 2 orders of magnitude greater than that of the monometallic analogue [Pt(tpy)(pic)]2+ for the same dsDNA sequence While exploring applications for the solid phase peptides, the major limitation encountered was the small quantities that were afforded by the loading of functional groups on the resin. To increase the amount of material that is available for electrochemical and spectroscopic studies, the synthetic approach was modified from solid phase to solution phase. Chapter 3 describes efforts focusing on the synthesis of a pyridine functionalized dipeptide that is reacted with platinum dipyridylthiophene ([Pt(dpt)]+1) ligand to cross-link the two pyridine groups forming a monometallic dipeptide. The placement of the Pt(dpt) on the peptide scaffold allows for potential applications as building blocks for labeling synthetic peptides with a luminescent and redox-active probe. Geometries that are more complex than the single strand allow for additional control over the assembly of supramolecular structures, including the potential for synthesizing heterometallic systems and reducing the opportunity for isomer and polymer formation. One of these geometries is the “hairpin” motif created through the functionalization of ferrocene mono- and dicarboxylic acid by aminoethylglycine (aeg) chains and further reacted with pendant pyridine or phenyl dipyridylamine ligands,presented in Chapter 4. Four distinct heterometallic structures are formed upon reaction with rhenium, each of which exhibits the characteristic redox properties of both the ferrocene moiety as well as the irreversible oxidative wave for the Re. The diffusion coefficients confirm that the Fc-Re structures are discrete assemblies and not coordination polymers. An alternate method to avoid isomer formation is the divergent approach taken from the preparation of dendrimers to synthesize symmetrical peptides, discussed in Chapter 5. These palindromic peptides offer a unique approach toward making duplexes that minimize the potential of both isomer and polymer formation. Preliminarily, a bipyridine (bpy) tripeptide is synthesized through this method and the subsequent duplex formed upon addition of Cu. The coordination geometry for the copper centers is probed through spectrophotometric titrations with different salts. Understanding the different structures formed is necessary for future work that will exploit the potential catalytic applications for these molecules.