The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in protection of human serum albumin carbonylation and cross-linking with methylglyoxal
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2014
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alpha-Oxoaldehydes, which are produced in higher quantities in diabetes, uremia, oxidative stress, inflammation and aging, react with the amino, guanidine and thiol groups of proteins and cause the formation of advanced glycated end-products and protein cross-linking. To prevent these reactions, the efficiency of tow molecular mass thiols with an alpha-amino-beta-mercapto-ethane group (Cys, penicillamine and N-acetylcysteine (NAcCys, with a blocked amino group)) as scavengers of methylglyoxal, compared with glutathione (GSH) and the biguanidine derivative metformin, was investigated. The time courses of the reactions of the aforementioned compounds with methylglyoxal were assayed. The reactivity of their thiol and amino groups decreased in the order of Cys gt penicillamine gt GSH gt NAcCys and penicillamine gt Cys gt GSH, respectively. Human serum albumin (HSA) carbonylation in the absence or presence of methylglyoxal scavengers were monitored by the determination of the amin...o, guanidine and thiol groups' contents, as well as by spectrofluorimetry, CD and native and SDS PAGE. Cys and penicillamine were highly efficient in the prevention of the carbonylation of the HSA-amino (for 80%) and guanidine (for 84% and 55%, respectively) groups and the formation of fluorescent AGEs. GSH and metformin exhibited medium efficiency (reduction of amino group's carbonylation for 60% and guanidine for about 30%); the least efficient was NAcCys. The presence of Cys, penicillamine and NAcCys led to an almost complete protection of the HSA-thiol group's carbonylation, whereas metformin was inefficient. The efficiency in the prevention of protein cross-linking increased in the order of metformin, NAcCys lt GSH lt penicillamine lt Cys. Thus, the substances with an alpha-amino-beta-mercapto-ethane group as a pharmacophore exhibit great potential as an efficient methylglyoxal scavengers, and are thus promising compounds for medicinal chemistry. In addition, they protect the HSA-SH group and preserve its antioxidative potential, which is very important for the HSA's function in vivo.
Izvor:
Molecular BioSystems, 2014, 10, 8, 2166-2175Izdavač:
- Royal Soc Chemistry, Cambridge
Finansiranje / projekti:
- Alergeni, antitela, enzimi i mali fiziološki značajni molekuli: dizajn, struktura, funkcija i značaj (RS-MESTD-Basic Research (BR or ON)-172049)
- Reinforcement of the Faculty of Chemistry, University of Belgrade, towards becoming a Center of Excellence in the region of WB for Molecular Biotechnology and Food research (EU-FP7-256716)
DOI: 10.1039/c4mb00217b
ISSN: 1742-206X
PubMed: 24899390
WoS: 000339135500015
Scopus: 2-s2.0-84903783815
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Aćimović, Jelena M. AU - Penezić, Ana Z. AU - Pavićević, Ivan D. AU - Jovanović, Vesna B. AU - Mandić, Ljuba M. PY - 2014 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1814 AB - alpha-Oxoaldehydes, which are produced in higher quantities in diabetes, uremia, oxidative stress, inflammation and aging, react with the amino, guanidine and thiol groups of proteins and cause the formation of advanced glycated end-products and protein cross-linking. To prevent these reactions, the efficiency of tow molecular mass thiols with an alpha-amino-beta-mercapto-ethane group (Cys, penicillamine and N-acetylcysteine (NAcCys, with a blocked amino group)) as scavengers of methylglyoxal, compared with glutathione (GSH) and the biguanidine derivative metformin, was investigated. The time courses of the reactions of the aforementioned compounds with methylglyoxal were assayed. The reactivity of their thiol and amino groups decreased in the order of Cys gt penicillamine gt GSH gt NAcCys and penicillamine gt Cys gt GSH, respectively. Human serum albumin (HSA) carbonylation in the absence or presence of methylglyoxal scavengers were monitored by the determination of the amino, guanidine and thiol groups' contents, as well as by spectrofluorimetry, CD and native and SDS PAGE. Cys and penicillamine were highly efficient in the prevention of the carbonylation of the HSA-amino (for 80%) and guanidine (for 84% and 55%, respectively) groups and the formation of fluorescent AGEs. GSH and metformin exhibited medium efficiency (reduction of amino group's carbonylation for 60% and guanidine for about 30%); the least efficient was NAcCys. The presence of Cys, penicillamine and NAcCys led to an almost complete protection of the HSA-thiol group's carbonylation, whereas metformin was inefficient. The efficiency in the prevention of protein cross-linking increased in the order of metformin, NAcCys lt GSH lt penicillamine lt Cys. Thus, the substances with an alpha-amino-beta-mercapto-ethane group as a pharmacophore exhibit great potential as an efficient methylglyoxal scavengers, and are thus promising compounds for medicinal chemistry. In addition, they protect the HSA-SH group and preserve its antioxidative potential, which is very important for the HSA's function in vivo. PB - Royal Soc Chemistry, Cambridge T2 - Molecular BioSystems T1 - The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in protection of human serum albumin carbonylation and cross-linking with methylglyoxal VL - 10 IS - 8 SP - 2166 EP - 2175 DO - 10.1039/c4mb00217b ER -
@article{ author = "Aćimović, Jelena M. and Penezić, Ana Z. and Pavićević, Ivan D. and Jovanović, Vesna B. and Mandić, Ljuba M.", year = "2014", abstract = "alpha-Oxoaldehydes, which are produced in higher quantities in diabetes, uremia, oxidative stress, inflammation and aging, react with the amino, guanidine and thiol groups of proteins and cause the formation of advanced glycated end-products and protein cross-linking. To prevent these reactions, the efficiency of tow molecular mass thiols with an alpha-amino-beta-mercapto-ethane group (Cys, penicillamine and N-acetylcysteine (NAcCys, with a blocked amino group)) as scavengers of methylglyoxal, compared with glutathione (GSH) and the biguanidine derivative metformin, was investigated. The time courses of the reactions of the aforementioned compounds with methylglyoxal were assayed. The reactivity of their thiol and amino groups decreased in the order of Cys gt penicillamine gt GSH gt NAcCys and penicillamine gt Cys gt GSH, respectively. Human serum albumin (HSA) carbonylation in the absence or presence of methylglyoxal scavengers were monitored by the determination of the amino, guanidine and thiol groups' contents, as well as by spectrofluorimetry, CD and native and SDS PAGE. Cys and penicillamine were highly efficient in the prevention of the carbonylation of the HSA-amino (for 80%) and guanidine (for 84% and 55%, respectively) groups and the formation of fluorescent AGEs. GSH and metformin exhibited medium efficiency (reduction of amino group's carbonylation for 60% and guanidine for about 30%); the least efficient was NAcCys. The presence of Cys, penicillamine and NAcCys led to an almost complete protection of the HSA-thiol group's carbonylation, whereas metformin was inefficient. The efficiency in the prevention of protein cross-linking increased in the order of metformin, NAcCys lt GSH lt penicillamine lt Cys. Thus, the substances with an alpha-amino-beta-mercapto-ethane group as a pharmacophore exhibit great potential as an efficient methylglyoxal scavengers, and are thus promising compounds for medicinal chemistry. In addition, they protect the HSA-SH group and preserve its antioxidative potential, which is very important for the HSA's function in vivo.", publisher = "Royal Soc Chemistry, Cambridge", journal = "Molecular BioSystems", title = "The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in protection of human serum albumin carbonylation and cross-linking with methylglyoxal", volume = "10", number = "8", pages = "2166-2175", doi = "10.1039/c4mb00217b" }
Aćimović, J. M., Penezić, A. Z., Pavićević, I. D., Jovanović, V. B.,& Mandić, L. M.. (2014). The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in protection of human serum albumin carbonylation and cross-linking with methylglyoxal. in Molecular BioSystems Royal Soc Chemistry, Cambridge., 10(8), 2166-2175. https://doi.org/10.1039/c4mb00217b
Aćimović JM, Penezić AZ, Pavićević ID, Jovanović VB, Mandić LM. The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in protection of human serum albumin carbonylation and cross-linking with methylglyoxal. in Molecular BioSystems. 2014;10(8):2166-2175. doi:10.1039/c4mb00217b .
Aćimović, Jelena M., Penezić, Ana Z., Pavićević, Ivan D., Jovanović, Vesna B., Mandić, Ljuba M., "The efficiency of compounds with alpha-amino-beta-mercapto-ethane group in protection of human serum albumin carbonylation and cross-linking with methylglyoxal" in Molecular BioSystems, 10, no. 8 (2014):2166-2175, https://doi.org/10.1039/c4mb00217b . .