The Photophysics and Photochemistry of the Near‐uv Absorbing Amino Acids–i. Tryptophan and Its Simple Derivatives

Creed, David

doi:10.1111/j.1751-1097.1984.tb03890.x

Cited by 473 publications

(158 citation statements)

References 234 publications

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“…UV light is absorbed by tryptophan and tyrosine in proteins at 310 nm and 290 nm, respectively [42,43]. The most effective wavelength, within the UVB range, for inducing DNA photoproducts in the basal layer of the epidermis is 300 nm [41].…”

Section: Introduction Introduction Introduction Introductionmentioning

confidence: 99%

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

Masuma

Kashima

Kurasaki

et al. 2013

Journal of Photochemistry and Photobiology B: Biology

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Ultraviolet (UV) radiations present in sunlight are a major etiologic factor for many skin diseases and induce DNA damage through formation of cyclobutane pyrimidine dimer (CPD). This study was conducted to determine the toxicological effects of different wavelengths (250, 270, 290, and 310 nm) and doses of UV radiation on cell viability, DNA structure, and DNA damage repair mechanisms in a PC12 cell system. For this, we evaluated cell viability and CPD formation. Cell survival rate was markedly decreased 24 h after UV irradiation in a dose-dependent manner at all wavelengths (except at 310 nm). Cell viability increased with increasing wavelength in the following order: 250 < 270 < 290 < 310 nm. UV radiation at 250 nm showed the highest cell killing ability, with a median lethal dose (LD50) of 120 mJ/cm2. The LD50 gradually increased with increase in wavelength. Among the 4 wavelengths tested, the highest LD50 (6000 mJ/cm2) was obtained for 310 nm. CPD formation decreased substantially with increasing wavelength. Among the 4 wavelengths, the proportion of CPD formation was highest at 250 nm and lowest at 310 nm. On the basis of LD50 values for each wavelength, PC12 cells irradiated with UV radiation of 290 nm showed maximum DNA repair ability, whereas those irradiated with the 310-nm radiation did not show any repair ability. Toxicity of UV radiation varied with wavelengths and exposure doses

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Section: Introduction Introduction Introduction Introductionmentioning

confidence: 99%

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

Masuma

Kashima

Kurasaki

et al. 2013

Journal of Photochemistry and Photobiology B: Biology

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“…26 Of primary interest to the current paper is the photodegradation of tryptophan and cystine residues. The photodegradation of tryptophan residues has been studied extensively 27,28 and a number of photoproducts have been characterized, including the fluorescent products N-formylkynurenine and kynurenine. 1 An important feature of tryptophan photolysis is the potential for photoinduced electron transfer to nearby disulfide bridges 1 where disulfide reduction leads to a thiolate and a thiyl radical.…”

Section: Chemistry Of Photooxidationmentioning

confidence: 99%

Effect of pH and Light on Aggregation and Conformation of an IgG1 mAb

2012

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Abstract:During the purification process, monoclonal antibodies may be exposed to parts of UV-C (200 to 290 nm), UV-B (290 to 320 nm) and visible light (400 to 760 nm) under a variety of buffer and pH conditions. Together, these conditions can promote both chemical and physical degradation which may result in conformational changes. To examine this possibility, the impact of UV light on an IgG1 mAb at pH 3.5, 5 and 8 was studied at multiple protein concentrations. Exposure to 302 nm light resulted in a pH-dependent formation of high molecular weight species where the degree of oligomerization increased with increasing pH.Characterization by SDS-PAGE under reducing and non-reducing conditions, and SEC-MALS, revealed that the predominant species were non-reducible dimeric, trimeric and higher order oligomeric species which occurred through processes other than intermolecular disulfide bond showing the greatest degree of change in the β-sheet structure. Exposure to UV light resulted in aggregation with pH-dependent yields decreasing in the following order, 8.0>5.0>3.5, while the opposite trend was observed for conformational changes, with pH-dependent extents decreasing in the following order:3.5>5.0>8.0. These pH-dependent trends suggest that different strategies will be required to stabilize the protein against these modifications during processing.

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“…Tryptophan side chains also pose a potential site of posttranslational modification risk (35). We have experienced first-hand many examples of binding and activity loss upon tryptophan oxidation in the context of monoclonal antibodies.…”

Section: Improving Chemical and Physical Stabilitymentioning

confidence: 99%

Early Engineering Approaches to Improve Peptide Developability and Manufacturability

Furman

Chiu

Hunter

2014

AAPS J

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Abstract. Downstream success in Pharmaceutical Development requires thoughtful molecule design early in the lifetime of any potential therapeutic. Most therapeutic monoclonal antibodies are quite similar with respect to their developability properties. However, the properties of therapeutic peptides tend to be as diverse as the molecules themselves. Analysis of the primary sequence reveals sites of potential adverse posttranslational modifications including asparagine deamidation, aspartic acid isomerization, methionine, tryptophan, and cysteine oxidation and, potentially, chemical and proteolytic degradation liabilities that can impact the developability and manufacturability of a potential therapeutic peptide. Assessing these liabilities, both biophysically and functionally, early in a molecule's lifetime can drive a more effective path forward in the drug discovery process. In addition to these potential liabilities, more complex peptides that contain multiple disulfide bonds can pose particular challenges with respect to production and manufacturability. Approaches to reducing the disulfide bond complexity of these peptides are often explored with mixed success. Proteolytic degradation is a major contributor to decreased half-life and efficacy. Addressing this aspect of peptide stability early in the discovery process increases downstream success. We will address aspects of peptide sequence analysis, molecule complexity, developability analysis, and manufacturing routes that drive the decision making processes during peptide therapeutic development.

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The Photophysics and Photochemistry of the Near‐uv Absorbing Amino Acids–i. Tryptophan and Its Simple Derivatives

Cited by 473 publications

References 234 publications

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

Effect of pH and Light on Aggregation and Conformation of an IgG1 mAb

Early Engineering Approaches to Improve Peptide Developability and Manufacturability

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