Synthesis of Vitamin E-Carnosine (VECAR): New Antioxidant Molecule with Potential Application in Atherosclerosis

Astete, Carlos E.; Meador, Danielle S.; Spivak, David A.; Sabliov, Cristina M.

doi:10.1080/00397911.2011.632829

Cited by 6 publications

(5 citation statements)

References 62 publications

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“…Carnosine has been conjugated with several molecules, such as carbohydrates (cyclodextrins, trehalose, glucose, lactose, galactose) [34,171,172,173], antioxidants (Trolox, ascorbic acid) [174,175], drugs ( l -Dopa) [176], physiological cofactors (lipoic acid, biotin) [177,178,179] and many aliphatic and aromatic moieties [180,181,182,183].…”

Section: Substrate Derivatives Of Carnosine and Its Related Dipeptmentioning

confidence: 99%

Carnosinases, Their Substrates and Diseases

2014

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Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (β-alanyl-L-histidine) and homocarnosine (γ-aminobutyryl-L-histidine). Alterations of serum carnosinase (CN1) activity has been associated with several pathological conditions, such as neurological disorders, chronic diseases and cancer. For this reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF) has been questioned. The hydrolysis of imidazole-related dipeptides in prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases like PepD (EC 3.4.13.3), PepV (EC 3.4.13.19) and anserinase (EC 3.4.13.5). The review deals with the structure and function of this class of enzymes in physiological and pathological conditions. The main substrates of these enzymes, i.e., carnosine, homocarnosine and anserine (β-alanyl-3-methyl-L-histidine) will also be described.

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Section: Substrate Derivatives Of Carnosine and Its Related Dipeptmentioning

confidence: 99%

Carnosinases, Their Substrates and Diseases

2014

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“…The length of the alkyl spacer (n) of the synthesized VECAR molecules varied from 4 to 22 [17]. In the present MD simulation study we specifically chose the shortest (n=4) and the longest (n=22) chain lengths that have been synthesized and an additional medium (n=13) chain length to investigate the dependence on the chain length.…”

Section: Simulation Methodologymentioning

confidence: 99%

“…In this study, we report the results of molecular dynamics simulations of bulk and aqueous solutions of a novel class of bolaamphiphiles, synthesized recently, called VECAR [17]. VECAR molecules are obtained by linking the head group of α-tocopherol and carnosine derivative with a single hydrocarbon chain [17] and have the structure and properties of asymmetric bolaamphiphiles with hydrophobicity that can be tailored for specific applications by varying the length of the hydrocarbon chain.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, they are nontoxic, have antioxidant properties, and environmentally are safe surfactants [17]. Despite their potential in various medical applications such as prevention of oxidative stress-related diseases and atherosclerosis, or as a genetic vehicle for delivery of a wide array of therapeutic compounds through the lipoprotein transport mechanisms [17], the bulk properties of VECAR are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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The role of the asymmetric bolaamphiphilic character of VECAR on the kinetic and structural aspects of its self-assembly: A molecular dynamics simulation study

Kim

Novak

Shrestha

et al. 2017

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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VECAR are novel bolaamphiphilic molecules consisting of two hydrophilic molecular groups, a carnosine derivative and a chromanol group, covalently linked by a hydrophobic alkyl spacer of varying length. Despite the potential for application in various biomedical applications VECAR properties, including their bulk properties, are still largely unknown. The early stage of the self-assembly process of VECAR molecules in water is studied using molecular dynamics simulations. The study reveals that the length of the hydrophobic spacer in VECAR affects the aggregation kinetics as well as the size, shape, density, and atomistic structure of the self-assembled aggregates. A mechanism based on cooperative interactions between water, the hydrophilic hydroxyl group, and the hydrophobic benzene ring of the chromanol head is proposed to explain the ordered packings of chromanols in the self-assembled aggregate structures at the aggregate-water interface.

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“…Additional derivatives of carnosine able to significantly counteract oxidative stress phenomena are represented by carnosine derivatized with Trolox [ 142 ], vitamin E (VECAR) [ 143 ], or acetylsalicylic acid [ 110 ] as well as lipoilcarnosine [ 141 ], carnosine analogs containing NO-donor substructures [ 149 ], and amide derivatives [ 148 ]. The latter derivatives have also been shown to be able to regulate metal homeostasis [ 108 ].…”

Section: Increasing Carnosine Bioavailability Through Dds And/or Chem...mentioning

confidence: 99%

The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development

et al. 2023

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Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to 5 mM). Because of its well-demonstrated multimodal pharmacodynamic profile, which includes anti-aggregant, antioxidant, and anti-inflammatory activities, as well as its ability to modulate the energy metabolism status in immune cells, this dipeptide has been investigated in numerous experimental models of diseases, including Alzheimer’s disease, and at a clinical level. The main limit for the therapeutic use of carnosine is related to its rapid hydrolysis exerted by carnosinases, especially at the plasma level, reason why the development of new strategies, including the chemical modification of carnosine or its vehiculation into innovative drug delivery systems (DDS), aiming at increasing its bioavailability and/or at facilitating the site-specific transport to different tissues, is of utmost importance. In the present review, after a description of carnosine structure, biological activities, administration routes, and metabolism, we focused on different DDS, including vesicular systems and metallic nanoparticles, as well as on possible chemical derivatization strategies related to carnosine. In particular, a basic description of the DDS employed or the derivatization/conjugation applied to obtain carnosine formulations, followed by the possible mechanism of action, is given. To the best of our knowledge, this is the first review that includes all the new formulations of carnosine (DDS and derivatives), allowing a decrease or complete prevention of the hydrolysis of this dipeptide exerted by carnosinases, the simultaneous blood–brain barrier crossing, the maintenance or enhancement of carnosine biological activity, and the site-specific transport to different tissues, which then offers perspectives for the development of new drugs.

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Synthesis of Vitamin E-Carnosine (VECAR): New Antioxidant Molecule with Potential Application in Atherosclerosis

Cited by 6 publications

References 62 publications

Carnosinases, Their Substrates and Diseases

Carnosinases, Their Substrates and Diseases

The role of the asymmetric bolaamphiphilic character of VECAR on the kinetic and structural aspects of its self-assembly: A molecular dynamics simulation study

The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development

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