Unusually high α-proton acidity of prolyl residues in cyclic peptides

Abstract

<p>The acidity of the α-proton in peptides has an essential role in numerous biochemical reactions and underpins their stereochemical integrity which is critical to their biological function. We report here...</p>

Abnormal (Hydroxy)proline Deuterium Content Redefines Hydrogen Chemical Mass

“…Looking for other explanations, we considered radical reactions that can be initiated in proteins by mechanical stress. 19 In structurally stressed peptides, the acidities of the α-proton are higher in prolyls than other amino acid residues abundant in collagen, 20 and thus, the prolyl α-carbon is a likely site of hydrogen abstraction. As the C–D bond is stronger than the C–H bond, 21 deuterium atoms at α-carbons should be less likely to be abstracted and more readily attached to α-carbon radicals than hydrogen atoms.…”

Is Deuterium Fractionation a Major Controlling Factor in Human Metabolism and Cancer? An Essential Role for Proline

“…The cis-configuration is favored even more when the proline residue is preceded by an aromatic amino acid, especially tyrosine [27]. The rate of Xaa-Pro cis/trans isomerism is a rate-limiting step in protein folding [28].…”

Polyketopiperazines: triketopiperazines, tetraketopiperazines synthesis, reactions, bioactivities and applications

“…On the other hand, the acidity of the α-proton in cyclic peptides has a vital role in biochemical reactions with stereochemical control which is important for their biological activities. The acidity of TKPs is 10 6 -times more acidic than their DKP analogues due to the formation of aromatic transition state 62 during the creation of the TKP enolate derivative 148,125 (Figure 11). The triketopiperazine structure is considered as operational example of 1,4-addition reaction to enones or enals using chiral organo-catalysis (Scheme 13).…”