fulltext.study @t Gmail

Measuring the bioactivity and molecular conformation of typically globular proteins with phenothiazine-derived methylene blue in solid and in solution: A comparative study using photochemistry and computational chemistry ☆

Paper ID Volume ID Publish Year Pages File Format Full-Text
29882 44445 2016 12 PDF Available
Title
Measuring the bioactivity and molecular conformation of typically globular proteins with phenothiazine-derived methylene blue in solid and in solution: A comparative study using photochemistry and computational chemistry ☆
Abstract

•The bioactivities of biopolymers are related closely to three-dimensional structures.•The molecular conformations of biomacromolecules were perturbed by phenothiazine-derived agent.•Photochemical properties of tryptophan residues would largely be affected by methylene blue.•Pharmacological activities of phenothiazine-derived drugs should notably be interfered with globular proteins.

Methylene blue is a phenothiazine agent, that possesses a diversity of biomedical and biological therapeutic purpose, and it has also become the lead compound for the exploitation of other pharmaceuticals such as chlorpromazine and the tricyclic antidepressants. However, the U.S. Food and Drug Administration has acquired cases of detrimental effects of methylene blue toxicities such as hemolytic anemia, methemoglobinemia and phototoxicity. In this work, the molecular recognition of methylene blue by two globular proteins, hemoglobin and lysozyme was characterized by employing fluorescence, circular dichroism (CD) along with molecular modeling at the molecular scale. The recognition of methylene blue with proteins appears fluorescence quenching via static type, this phenomenon does cohere with time-resolved fluorescence lifetime decay that nonfluorescent protein–drug conjugate formation has a strength of 104 M− 1, and the primary noncovalent bonds, that is hydrogen bonds, π-conjugated effects and hydrophobic interactions were operated and remained adduct stable. Meantime, the results of far-UV CD and synchronous fluorescence suggest that the α-helix of hemoglobin/lysozyme decreases from 78.2%/34.7% (free) to 58.7%/23.8% (complex), this elucidation agrees well with the elaborate description of three-dimensional fluorescence showing the polypeptide chain of proteins partially destabilized upon conjugation with methylene blue. Furthermore, both extrinsic fluorescent indicator and molecular modeling clearly exhibit methylene blue is situated within the cavity constituted by α1, β2 and α2 subunits of hemoglobin, while it was located at the deep fissure on the lysozyme surface and Trp-62 and Trp-63 residues are nearby. With the aid of computational analyses and combining the wet experiments, it can evidently be found that the recognition ability of proteins for methylene blue is patterned upon the following sequence: lysozyme < hemoglobin < albumin. Basically, the distinction originates from different spatial structures of proteins and noncovalent interactions between proteins and methylene blue. In addition, biological relevance of the biorecognition of methylene blue with proteins was briefly discussed. We hope that this study could provide further standpoint so that one explore the biological activity of methylene blue and also phenothiazines.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
Ala, alanine; ANOVA, analysis of variance; ANS, 8-anilino-1-naphthalenesulfonic acid; CD, circular dichroism; DNA, deoxyribonucleic acid; Ile, isoleucine; IRF, instrument response function; Leu, leucine; Lys, lysine; Phe, phenylalanine; R, correlation coe
First Page Preview
Measuring the bioactivity and molecular conformation of typically globular proteins with phenothiazine-derived methylene blue in solid and in solution: A comparative study using photochemistry and computational chemistry ☆
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 158, May 2016, Pages 69–80
Authors
, , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us