Role of Surface Exposed Tryptophan as Substrate Generators for the Antibody Catalyzed Water Oxidation Pathway

Sreedhara, Alavattam; Lau, Kimberly S. F.; Li, Charlene; Hosken, Brian D.; Macchi, Frank; Zhan, Daqian; Shen, Amy; Steinmann, Daniel; Schöneich, Christian; Lentz, Yvonne

doi:10.1021/mp300418r

Cited by 51 publications

(67 citation statements)

References 44 publications

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“…Nonetheless, it has been shown that a hydroxyl radical generated in close proximity to the site of oxidation may be consumed before it can diffuse, which would render mannitol unable to quench the reaction. 42 Data from the Amplex red assay indicates that very little to no hydrogen peroxide was generated when the peptide was incubated with Cu 2C . The data from the bathocuproine assay showed only approximately 15% reduction of Cu 2C to Cu 1C , adding further support that single electron transfer and further generation of various ROS is not the major pathway in Cu 2C -mediated degradation of the hinge peptide.…”

Section: Discussionmentioning

confidence: 99%

Metal ion interactions with mAbs: Part 1

Glover

Basa²,

Moore

et al. 2015

mAbs

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(2015) Metal ion interactions with mAbs: Part 1, mAbs, 7:5, 901-911, DOI: 10.1080DOI: 10. /19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 , can bind to the mAb and undergo hydrolysis or oxidation, which can lead to cleavage of the molecule. To better understand the mechanism of Cu 2C -mediated mAb fragmentation, hinge region cleavage products and their rates of formation were studied as a function of pH with and without Cu 2C . More detailed analysis of the chemical changes was investigated using model linear and cyclic peptides (with the sequence of SCDKTHTC) derived from the upper hinge region of the mAb. Cu 2C mediated fragmentation was determined to be predominantly via a hydrolytic pathway in solution. The sites and products of hydrolytic cleavage are pH and strain dependent. In more acidic environments, rates of Cu 2C induced hinge fragmentation are significantly slower than at higher pH. Although the degradation reaction rates between the linear and cyclic peptides are not significantly different, the products of degradation vary. mAb fragmentation can be reduced by modifying His, which is a potential metal binding site and a known ligand in other metalloproteins. These results suggest that a charge may contribute to stabilization of a specific molecular structure involved in hydrolysis, leading to the possible formation of a copper binding pocket that causes increased susceptibility of the hinge region to degradation.

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Section: Discussionmentioning

confidence: 99%

Metal ion interactions with mAbs: Part 1

Glover

Basa²,

Moore

et al. 2015

mAbs

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“…However, four amino acids; methionine, cysteine, tryptophan and histidine were found to catalyze ozone formation in the presence of singlet oxygen (Yamashita et al, 2008). The common feature of these amino acids is that they are all photooxidizable (Wentworth et al, 2001) as evidenced through numerous studies both in free form and as components of proteins (Zhu et al, 2004;Pattison et al, 2012;Lundeen and McNeill, 2013;Sreethara et al, 2013;Amano et al, 2014;Liu et al, 2014).…”

Section: Water Oxidation Pathwaymentioning

confidence: 99%

“…Despite only a few amino acids being oxidized in the presence of singlet oxygen, they are able to generate adequate ozone and hydrogen peroxide (Sreethara et al, 2013). Therefore, it is possible to mention that protein molecules lacking these amino acids are not able to generate ozone.…”

Section: Water Oxidation Pathwaymentioning

confidence: 99%

Reactive oxygen species (ROS) generation, impacts on tissue oxidation and dietary management of non-communicable diseases: A review

Wafula¹,

Arnold²,

Calvin³

et al. 2017

Afr. J. Biochem. Res.

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Generation of reactive oxygen species (ROS) in biological systems has been reported to be a significant cause of inflammatory and metabolic diseases. More recently, ROS and in a particular ozone has also been implicated in the conversion of cholesterol to atherogenic compounds, secosterol A, and upon aldolization to secosterol-B. Secosterol-A is uniquely produced by cholesterol ozonolysis, while secosterol-B can also be generated through the reaction of cholesterol with singlet oxygen. On the other hand, lipid oxidation reactions generate hydroperoxides, which upon catalytic and/or enzymatic decomposition yields lipid peroxide products of significant importance to tissue health. The mechanism of formation of potent oxidants like ozone in biological systems has not been clearly demonstrated, with only a theory: That antibodies catalyze oxidation of water by singlet oxygen to yield a trioxidic species, like hydrogen trioxide, as an intermediate in hydrogen peroxide formation while a recent hypothesis indicates that ozone could also be an intermediate in the aforementioned pathway and could be generated from biological molecules in the presence of singlet oxygen. Similarly, there is new information being generated concerning the involvement of antioxidants and amino acids in either termination or propagation of oxidative processes in mammalian systems. This review explores mechanisms of ROS/ozone generation in tissues, lipid peroxidation, cholesterol oxidation and highlight dietary management of non-communicable diseases with a focus on the roles of antioxidants and amino acids.

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“…Another recent publication focuses on the role of exposed Trps on the surface of antibodies that results in the generation of reactive oxygen species such as singlet oxygen and superoxides upon exposure to light (Sreedhara et al, 2013). In particular, antibodies are capable of catalyzing a water oxidation pathway termed the antibody-catalyzed water oxidation pathway (Wentworth et al, 2001), and surface-exposed Trps in the antibody during exposure to light catalyze this process (Figure 3.8(a)).…”

Section: Trp Oxidation In Mabsmentioning

confidence: 99%

“…Samples: 1 = T0; 2 = 24 h; 3 = 48 h; 4 = 72 h; and 5 = 96 h light exposure under ICH guidelines. Reproduced fromSreedhara et al (2013).…”

mentioning

confidence: 99%