Structural and Functional Consequences of the Weak Binding of Chlorin e6 to Bovine Rhodopsin

Mitchell, James; Yanamala, Naveena; Tan, Yi; Gardner, Eric E.; Tirupula, Kalyan; Balem, Fernanda; Sheves, Mordechai; Nietlispach, Daniel; Klein‐Seetharaman, Judith

doi:10.1111/php.13074

Cited by 3 publications

(4 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The formation of Ce6/Rh binding sites confirms recent in vivo studies, conducted through terahertz spectroscopy 53 and 19 F NMR experiments, 54 and could partially explain the in vitro enhancement of Rh thermal stability in the presence of Ce6. 55 Analysis of the structural properties of the Ce6/Rh complexes already sheds light on some hypotheses regarding the photophysical pathways that lead to RET isomerization.…”

supporting

confidence: 86%

“…The formation of Ce6/Rh binding sites confirms recent in vivo studies, conducted through terahertz spectroscopy and 19 F NMR experiments, and could partially explain the in vitro enhancement of Rh thermal stability in the presence of Ce6 …”

supporting

confidence: 85%

“…Increasing the sensitivity of the visual apparatus to the IR radiation, also through its interaction with external drugs, is particularly fascinating and can also shed light on particular evolutionary pathways of organisms adapting to extreme conditions. For instance, the enhancement of red vision in dragon fish exposed to the presence of Ce6 has been ascribed by some authors to allosteric modulation of G-protein coupled receptors in dragon fish, also suggesting a peculiar evolutionary event. − …”

mentioning

confidence: 99%

See 2 more Smart Citations

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Marazzi

Gattuso

Giussani

et al. 2019

J. Phys. Chem. Lett.

View full text Add to dashboard Cite

In humans, vision is limited to a small fraction of the whole electromagnetic spectrum. One possible strategy for enhancing vision in deep-red or poor-light conditions consists of recruiting chlorophyll derivatives in the rod photoreceptor cells of the eye, as suggested in the case of some deep-sea fish. Here, we employ all-atom molecular simulations and high-level quantum chemistry calculations to rationalize how chlorin e6 (Ce6), widely used in photodynamic therapy although accompanied by enhanced visual sensitivity, mediates vision in the dark, shining light on a fascinating but largely unknown molecular mechanism. First, we identify persistent interaction sites between Ce6 and the extracellular loops of rhodopsin, the transmembrane photoreceptor protein responsible for the first steps in vision. Triggered by Ce6 deep-red light absorption, the retinal within rhodopsin can be isomerized thus starting the visual phototransduction cascade. Our data largely exclude previously hypothesized energy-transfer mechanisms while clearly lending credence to a retinal isomerization indirectly triggered by singlet oxygen, proposing an alternative mechanism to rationalize photosensitizermediated night vision.

show abstract

supporting

confidence: 86%

supporting

confidence: 85%

mentioning

confidence: 99%

See 1 more Smart Citation

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Marazzi

Gattuso

Giussani

et al. 2019

J. Phys. Chem. Lett.

View full text Add to dashboard Cite

show abstract

“…There, it may act as an allosteric modulator, perhaps via some mechanism mediated by radicals. [ 194–198 ]…”

Section: Light‐activated Biomedical Applications Of Chlorophyll Derivativesmentioning

confidence: 99%

Light‐Activated Biomedical Applications of Chlorophyll Derivatives

Pucci

Martinelli

Degl’Innocenti

et al. 2021

Macromolecular Bioscience

View full text Add to dashboard Cite

Tetrapyrroles are the basis of essential physiological functions in most living organisms. These compounds represent the basic scaffold of porphyrins, chlorophylls, and bacteriochlorophylls, among others. Chlorophyll derivatives, obtained by the natural or artificial degradation of chlorophylls, present unique properties, holding great potential in the scientific and medical fields. Indeed, they can act as cancer‐preventing agents, antimutagens, apoptosis inducers, efficient antioxidants, as well as antimicrobial and immunomodulatory molecules. Moreover, thanks to their peculiar optical properties, they can be exploited as photosensitizers for photodynamic therapy and as vision enhancers. Most of these molecules, however, are highly hydrophobic and poorly soluble in biological fluids, and may display undesired toxicity due to accumulation in healthy tissues. The advent of nanomedicine has prompted the development of nanoparticles acting as carriers for chlorophyll derivatives, facilitating their targeted administration with demonstrated applicability in diagnosis and therapy. In this review, the chemical and physical properties of chlorophyll derivatives that justify their usage in the biomedical field, with particular regard to light‐activated dynamics are described. Their role as antioxidants and photoactive agents are discussed, introducing the most recent nanomedical applications and focusing on inorganic and organic nanocarriers exploited in vitro and in vivo.

show abstract

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

2021

View full text Add to dashboard Cite

Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin–macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.

show abstract

Structural and Functional Consequences of the Weak Binding of Chlorin e6 to Bovine Rhodopsin

Cited by 3 publications

References 63 publications

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Light‐Activated Biomedical Applications of Chlorophyll Derivatives

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

Contact Info

Product

Resources

About