There are several groups who published in this area (see ref. below).

They generally have two ideas:

1) intramolecular electron transfer (in your case tyrosyl radicals (Tyr-O(·)) will be stabilized and/or propagated down the peptide chain;

2) Change in pKa and oxidation potential.

Best regards, Sergey.

A. Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: computer simulation studies in model tyrosine-cysteine peptides in solution. Arch Biochem Biophys. 2012 Sep 1;525(1):82-91. Petruk AA, Bartesaghi S, Trujillo M, Estrin DA, Murgida D, Kalyanaraman B, Marti MA, Radi R.

B. The effect of neighboring methionine residue on tyrosine nitration and oxidation in peptides treated with MPO, H2O2, and NO2(-) or peroxynitrite and bicarbonate: role of intramolecular electron transfer mechanism? Arch Biochem Biophys. 2009 Apr 15;484(2):134-45. Zhang H, Zielonka J, Sikora A, Joseph J, Xu Y, Kalyanaraman B.

C. Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res. 2013 Feb 19;46(2):550-9. Radi R.

D. Moving a phenol hydroxyl group from the surface to the interior of a protein: effects on the phenol potential and pK(A). Biochemistry. 2005 Sep 6;44(35):11891-902. Hay S, Westerlund K, Tommos C.

I presume your number reports on the oxidation of tyrosine to the radical, which would be accompanied by deprotonation of the phenolic oxygen. A ~200 mV difference means that the oxidation of a tyrosine is ~4.6 kcal/mol more difficult in the folded peptide.. That might be a strong hydrogen bond from the phenolic hydrogen of tyrosine to - who knows? Is there a reason to expect a strong hydrogen-bond? If you know the structure of the folded peptide, or have a plausible model, you could change residues that could make strong interactions to possibly special tyrosines.

Greetings Teodor

Negative shift (blue shift) for Tyr residue demonstrate that the microenvironment of Tyr are more nonpolar and this residue was buried in to the core of protein, therefore the protein structure maybe fold.

the one-electron redox potentials of residues might vary with their environment. for methionine we have shown that it varies with the geometry (by DFT methods). For tyrosine there was a lot of measurements which all lead to very close values of the reodox potentials: ca. 0.9V vs ENH. However we got funny results about intramolecular long range electron transfer between methionine and tyrosine that are strange: in a peptide (met enkephalin) the met•+ led to TyrO•quantitatively while in CFP there was not a single electron transfer between the same residues although some of them were quite close to each other. We did not interprete this result but it might be a thermodynamical reason of variation of the redox potentials. So I have similar observations to yours.

Thank you very much for your answers. I did the same experiment using another structure in which only the tyrosine where substituted with phenylalanine, and I get the same peak, at 0.4. It remains histidine or methionine or something else but I am more for something else since the oxidation potential of both his and met is around 1V.