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The initial goal of this project was to design “synzymes;” synthetic peptides that possessed enzymatic-like properties.  As a target we were attempting to design Mn-containing prophyrin peptides that were held within a peptide-peptide nucleic acid (pPNA) scaffolf.  The PNA portion was used to maintain a cavity about the peptide portion, which in turn contained the Mn-porphyrin.  We successfully prepared the initial target (pPNA-Mn¹), which contained the Mn(III)-porphyrin within a stable fold.  The axial ligand to Mn(III) was derived from an amino-acid within the peptide portion of the pPNA, and was either a: phenolate (from a tyrosine), an imidazole (from a histidine) or a thioate (from a cysteinate).  These peptides were characterized by: X-ray absorption, electronic absorption and circular dichroism spectroscopies.   Although successfully prepared, we found that the pPNA “catalyst” was not sufficiently stable to perform oxidation reactions; addition of peroxide (to effect a peroxide-shunt like mechanism) yielded rapid decomposition of the pPNA-Mn¹ into intractable materials.  Variation of the peptide scaffold in an attempt to provide for a more robust peptide backbone proved futile;  even changing the backbone to all aliphatic residues still resulted in rapid decomposition of the peptide.  We are currently writing these data up for publication in early to mid 2012.

Thus we turned our attentions to the creation of synthetic myoglobins.  This has practical applications in the preparation of synthetic blood, and may also give insight into the limitations of the creation of synthetic pPNA oxidation synzymes. Two pPNA segments were prepared.   One had Fe-protopophyrin-IX covalently bound to an N-terminal lysine residue, while the other had a histidine residue to bind the Fe-center.  A smaller PNA segment was utilized than before (the Dickerson dodecomer sequence was not used) that provided excellent stability through PNA base pairing and easier synthesis/purification.  We placed a tryptophan residue to provide hydrogen-bonding to O₂ in the peptide sequence in such a manner that it would a) provide stability to the bound O₂, b) not coordinate to the Fe-center and c) disrupt the binding of other ligands.  It was found that we could reversibly bind O₂ in water as a function of O₂ pressure and disfavor N₃^– and NO binding.  CO binding was found to not be disrupted.  We are currently writing this up for rapid communication in early 2012.