Peptides hydrogen abstraction

Hydrogen abstraction by ketone sensitizers forms the basis of an elegant alkylation procedure for ethers, amides, lactones, amino acids, and peptides developed by Elad and his group.94 Terminal olefins, for example, can be added to y-butyrolactone (15) in good yield.95... 

ThiyI radicals are important reactants in several enzymes and form in vivo during conditions of oxidative stress [6]. They have been considered for a long time as rather unreactive species. However, recently several reactions of thiyi radicals with biomolecules have been described (catalysis olcis-trans isomerization of unsaturated fatty acids, addition to the pyrimidine bases C5-C6 double bonds, and hydrogen abstraction from polyunsaturated fatty acid, thymine and peptide C -H and side chain C-H bonds) [7]. More recently, the intramolecular addition of peptide cysteine thiyi radicals (CysS ) to phenylalanine (Phe) yielding alkylothio-substituted cyclohexadienyl radicals was demonstrated in the peptides Phe-Cys and Phe-Gly-Cys-Gly (Fig. 2) [8]. 

In general, sulfide radical cations would either deprotonate in the a-position to the sulfur, yielding a-(alkylthio)alkyl radicals, or engage in the one-electron oxidation of additional substrates. However, recent hypothesis and results have focused on a possible role of methionine sulfide radical cations in hydrogen abstraction reactions within the Alzheimer s disease yS-amyloid peptide (ySAP) [73]. These mechanisms will be discussed here in some detail. 

Electron Donation Ionization, OH-Adduct Formation, and Hydrogen Abstraction. Ionization of amino acids or peptides either through photolysis or radiolysis leads to cation radicals, the fate of which will be influenced by the nature of the compound and the medium. 

Abstraction of H from the Peptide by Carbon Radicals. The carbon radicals derived from deamination, deamidation, and decarboxylation react subsequently with the peptides to abstract hydrogen, forming the more stable a-carbon peptide radicals (63). This reaction can be demonstrated in irradiated ices containing acetylamino acids. Continuing with the N-acetylalanine example, one can also see in Figure 7 that upon further annealing to — 50 °C, another radical appears corresponding to reaction 19 ... 

In peptides, amino acids are joined by peptide bonds to form the polypeptide chain. The e q, OH, and H radicals react with the amino acids and with the polypeptide chain with high rate coefficients that are close to the diffusion limit. OH radicals and, less frequently, H atoms abstract a hydrogen atom from the polypeptide chain (from the carbon atoms) or from the side chains, but they can also add to the rings of the aromatic amino acids. The radical site produced on the main chain may move along the chain by an internal hydrogen abstraction mechanism. If the H atom is abstracted from an S-H bond the radical migration stops, since the S-H bond is much weaker than the G-H bonds. This reaction is the basis of repair mechanism. The radicals may terminate in radical-radical reactions. 

Fig. 19 Another proposed mechanism of peptide synthesis catalyzed by the ribosome. The P-site 2 -OH group abstracts a hydrogen from the amino group [161]...

For the first two peptides, CysS radicals abstract hydrogen atoms from the or-carbon of glycine with 7 = (1.0 to 1.1) x 10 s , while the reverse reaction proceeds with = (8.0 to 8.9) x 10 s . For the latter peptide, CysS radicals abstract hydrogen atoms from the ce-carbon of alanine with = (0.9 to 1.0) x 10 s while the reverse reaction proceeds with k -j = 1.0 x 10 s" The order of reactivity, Gly > Ala, is in accordance with previous studies on intermolecular reactions of thiyl radicals with these amino acids. The fact that < k y suggests that some secondary structure prevents the adoption of extended conformations for which calculations of homolytic bond dissociation energies would have predicted k j > k y. 

Nauser T, Schoneich C. (2003) Thiyl radicals abstract hydrogen atoms from the aC-H bonds in model peptides Absolute rate constants and effect of amino acid structure. / Am Chem Soc 125 2042-2043. 

---