Influence of amino acid relative position on the oxidative modification of histidine and glycine peptides

Reis, Ana; Fonseca, Conceição; Maciel, Elisabete; Domingues, Pedro; Domingues, M. Rosário M.

doi:10.1007/s00216-011-4668-1

Cited by 6 publications

(4 citation statements)

References 50 publications

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“…Its quenching activity is not yet described but Reis et al (2011) recently demonstrated that GH peptide (along with other glycine and histidine-containing di-and tripeptides) is highly susceptible to oxidative reactions yielding cyclic endoperoxides and azetidinone derivatives. Other histidinecontaining dipeptides have been described in literature with different chemical and/or biological applications, even though their quenching activity has never been assayed.…”

Section: Carnosine Bioavailability and Metabolic Fate In Humansmentioning

confidence: 98%

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Vistoli

Carini

2012

Amino Acids

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The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

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Section: Carnosine Bioavailability and Metabolic Fate In Humansmentioning

confidence: 98%

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Vistoli

Carini

2012

Amino Acids

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“…Studies examining abiotic processes (e.g., photochemical transformation and sorption) of free His provide a suitable foundation to further our understanding of His photooxidation in the context of higher order structures (i.e., DCAAs). Previous studies have suggested that the photolabile residues exclusively dominated the photoreactivity of oligopeptides. − However, other studies argued that the neighboring photostable residues and the relative position of photolabile residues within the sequence also influence the reactivity of oligopeptides. ,− For instance, the neighboring photostable AA residues may induce a shift in the p K a value of a photolabile residue, which subsequently affects the photoreactivity of DCAAs. Shifts in the p K a values of AAs and the underlying mechanisms that result in these shifts have been extensively studied by biochemists. − The conformation, functionality, and stability of many oligopeptides and proteins are tied to structure-dependent alterations of AA p K a values. − Likewise, the environmental photoreactivities of DCAAs are expected to vary depending on the p K a values of their constituent photolabile residues, especially for AAs that have environmentally relevant p K a values, namely histidine.…”

Section: Introductionmentioning

confidence: 99%

Assessing the Indirect Photochemical Transformation of Dissolved Combined Amino Acids through the Use of Systematically Designed Histidine-Containing Oligopeptides

Chu

Lundeen

Sander

et al. 2015

Environ. Sci. Technol.

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Photooxidation is an important abiotic transformation pathway for amino acids (AAs) in sunlit waters. Although dissolved free AAs are well studied, the photooxidation of dissolved combined AAs (DCAAs) remains poorly investigated. This study is a systematic investigation of the effect of neighboring photostable AA residues (i.e., aliphatic, cationic, anionic, or aromatic residues) on the environmental indirect photochemical transformation of histidine (His) in His-containing oligopeptides. The pKa values of His residues in the studied oligopeptides were found to be between 4.3 and 8.1. Accordingly, the phototransformation rate constants of the His-containing oligopeptides were highly pH-dependent in an environmentally relevant pH range with higher reactivity for neutral His than for the protonated species. The photostable AA residues significantly modulated the photoreactivity of oligopeptides either through altering the accessibility of His to photochemically produced oxidants or through shifting the pKa values of His residues. In addition, the influence of neighboring photostable AA residues on the sorption-enhanced phototransformation of oligopeptides in solutions containing chromophoric dissolved organic matter (CDOM) was assessed. The constituent photostable AA residues promoted sorption of His-containing oligopeptides to CDOM macromolecules through electrostatic attraction, hydrophobic effects, and/or low-barrier hydrogen bonds, and subsequently increased the apparent phototransformation rate constants by up to 2 orders of magnitude.

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“…Together, these findings may suggest a structural rearrangement of the V H domain, proximal to the heavy chain CDRs, in which all four of these side-chains have altered solvent accessibility as a result of the WFL-STT substitutions. However, recent evidence suggests that side-chain microenvironment and amino acid sequence can play a significant role in determining the degree to which side-chains are susceptible to radical oxidation. ,, The W30S, F31T, and L57T substitutions are expected to decrease the reactivity to hydroxyl radical labeling of these individual amino acid positions by factors of 40, 13, and 3, respectively . This likely explains the absence of modification for two of the equivalent amino acid positions in STT (S30 and T31; residue 57 labels in neither variant).…”

Section: Resultsmentioning

confidence: 99%

Long-Range Conformational Changes in Monoclonal Antibodies Revealed Using FPOP-LC-MS/MS

et al. 2019

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Differences in conformational dynamics between two full-length monoclonal antibodies have been probed in detail using Fast Photochemical Oxidation of Proteins (FPOP) followed by proteolysis and LC-ESI-MS/MS analyses. FPOP uses hydroxyl radical labeling to probe the surface-accessible regions of proteins and has the advantage that the resulting covalent modifications are irreversible, thus permitting optimal downstream analysis. Despite the two monoclonal antibodies (mAbs) differing by only three amino acids in the heavy chain complementarity determining regions (CDRs), one mAb, MEDI1912-WFL, has been shown to undergo reversible self-association at high concentrations and exhibited poor pharmacokinetic properties in vivo, properties which are markedly improved in the variant, MEDI1912-STT. Identifying the differences in oxidative labeling between the two antibodies at residue level revealed long-range effects which provide a key insight into their conformational differences. Specifically, the amino acid mutations in the CDR region of the heavy chain resulted in significantly different labeling patterns at the interfaces of the CL–CH1 and CH1–CH2 domains, with the nonaggregating variant undergoing up to four times more labeling in this region than the aggregation prone variant, thus suggesting a change in the structure and orientation of the CL–CH1 interface. The wealth of FPOP and LC-MS data obtained enabled the study of the LC elution properties of FPOP-oxidized peptides. Some oxidized amino acids, specifically histidine and lysine, were noted to have unique effects on the retention time of the peptide, offering the promise of using such an analysis as an aid to MS/MS in assigning oxidation sites.

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Influence of amino acid relative position on the oxidative modification of histidine and glycine peptides

Cited by 6 publications

References 50 publications

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Assessing the Indirect Photochemical Transformation of Dissolved Combined Amino Acids through the Use of Systematically Designed Histidine-Containing Oligopeptides

Long-Range Conformational Changes in Monoclonal Antibodies Revealed Using FPOP-LC-MS/MS

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