TY - JOUR

T1 - Photocaging of amino acids and short peptides by arylidenethiazoles: mechanism, photochemical characteristics and biological behaviour

AU - Gagarin, Aleksey A.

AU - Minin, Artem S.

AU - Shevyrin, Vadim A.

AU - Benassi, Enrico

AU - Belskaya, Nataliya P.

N1 - Research funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Development Programme within the Priority 2030 Programme) is gratefully acknowledged. This work was performed using the equipment of the Shared Research Centre of Scientific Equipment SRC IIP UrB RAS. The computational resources were kindly offered by the HPCC at the Nazarbayev University.

PY - 2024/9/28

Y1 - 2024/9/28

N2 - A series of fluorophores based on the (5-methyl-4-phenylthiazol-2-yl)-3-phenylacrylonitrile (MPTA) core were designed and synthesised for photocaging of amino acids and peptides. The photophysical characteristics of these compounds and their hybrids with biomolecules were thoroughly investigated through a joint experimental, spectral and computational approach. The photorelease ability of the obtained amino acids-MPTA and peptides-MPTA hybrids was studied under various conditions, including different UV irradiation wavelength and power, and solvents. The main reaction products were identified using high-performance liquid chromatography combined with high-resolution mass spectrometry. Photo uncaging kinetics was quantitatively studied using absorption spectroscopy. The mechanism of photorelease of amino acids and peptides was elucidated through quantum mechanical calculations, which were also used for the exploration of photophysical properties of the excited states, and photodissociation energetics quantification. Relationships between the structure of fluorophores and photodissociation characteristics were estimated, and fluorophores with the good uncaging characteristics (biomolecule photoreleasing yield, uncaging rate, and effectiveness) were identified. Cell viability assays using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT showed a low cytotoxicity of the hybrids. Confocal microscopy revealed the easy penetration of the hybrids into living cells and their selective accumulation in the endoplasmic reticulum, lipid droplets and mitochondria, depending on their chemical structure.

AB - A series of fluorophores based on the (5-methyl-4-phenylthiazol-2-yl)-3-phenylacrylonitrile (MPTA) core were designed and synthesised for photocaging of amino acids and peptides. The photophysical characteristics of these compounds and their hybrids with biomolecules were thoroughly investigated through a joint experimental, spectral and computational approach. The photorelease ability of the obtained amino acids-MPTA and peptides-MPTA hybrids was studied under various conditions, including different UV irradiation wavelength and power, and solvents. The main reaction products were identified using high-performance liquid chromatography combined with high-resolution mass spectrometry. Photo uncaging kinetics was quantitatively studied using absorption spectroscopy. The mechanism of photorelease of amino acids and peptides was elucidated through quantum mechanical calculations, which were also used for the exploration of photophysical properties of the excited states, and photodissociation energetics quantification. Relationships between the structure of fluorophores and photodissociation characteristics were estimated, and fluorophores with the good uncaging characteristics (biomolecule photoreleasing yield, uncaging rate, and effectiveness) were identified. Cell viability assays using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT showed a low cytotoxicity of the hybrids. Confocal microscopy revealed the easy penetration of the hybrids into living cells and their selective accumulation in the endoplasmic reticulum, lipid droplets and mitochondria, depending on their chemical structure.

KW - Humans

KW - Peptides/chemistry

KW - Amino Acids/chemistry

KW - Cell Survival/drug effects

KW - Photochemical Processes

KW - Thiazoles/chemistry

KW - Molecular Structure

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85205869639&origin=inward&txGid=a0840e8398278f20e159e7d0208096fb

UR - https://www.mendeley.com/catalogue/202a2932-6ae6-3a2c-a2df-6ec0325dcf62/

U2 - 10.1039/d4tb01441c

DO - 10.1039/d4tb01441c

M3 - Article

C2 - 39378025

VL - 12

SP - 11402

EP - 11413

JO - Journal of Materials Chemistry B

JF - Journal of Materials Chemistry B

SN - 2050-750X

IS - 44

ER -