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  1. Article: Influence of Desialylation on the Drug Binding Affinity of Human Alpha-1-Acid Glycoprotein Assessed by Microscale Thermophoresis.

    Šeba, Tino / Kerep, Robert / Weitner, Tin / Šoić, Dinko / Keser, Toma / Lauc, Gordan / Gabričević, Mario

    Pharmaceutics

    2024  Volume 16, Issue 2

    Abstract: Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. The sialic acid groups that terminate the N-glycan chains of AAG have been ... ...

    Abstract Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. The sialic acid groups that terminate the N-glycan chains of AAG have been reported to change in response to numerous health conditions and may have an impact on the binding of drugs to AAG. In this study, we quantified the binding between native and desialylated AAG and seven drugs from different pharmacotherapeutic groups (carvedilol, diltiazem, dipyridamole, imipramine, lidocaine, propranolol, vinblastine) using microscale thermophoresis (MST). This method was chosen due to its robustness and high sensitivity, allowing precise quantification of molecular interactions based on the thermophoretic movement of fluorescent molecules. Detailed glycan analysis of native and desialylated AAG showed over 98% reduction in sialic acid content for the enzymatically desialylated AAG. The MST results indicate that desialylation generally alters the binding affinity between AAG and drugs, leading to either an increase or decrease in
    Language English
    Publishing date 2024-02-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics16020230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics?

    Kerep, Robert / Šeba, Tino / Borko, Valentina / Weitner, Tin / Keser, Toma / Lauc, Gordan / Gabričević, Mario

    International journal of molecular sciences

    2023  Volume 24, Issue 10

    Abstract: Human serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N-glycan chains of ...

    Abstract Human serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N-glycan chains of alpha-1 acid glycoprotein change in response to certain health conditions and may have a major impact on drug binding to alpha-1 acid glycoprotein. The interaction between native or desialylated alpha-1 acid glycoprotein and four representative drugs-clindamycin, diltiazem, lidocaine, and warfarin-was quantitatively evaluated using isothermal titration calorimetry. The calorimetry assay used here is a convenient and widely used approach to directly measure the amount of heat released or absorbed during the association processes of biomolecules in solution and to quantitatively estimate the thermodynamics of the interaction. The results showed that the binding of drugs with alpha-1 acid glycoprotein were enthalpy-driven exothermic interactions, and the binding affinity was in the range of 10
    MeSH term(s) Humans ; Protein Binding ; Warfarin/pharmacology ; Clindamycin ; Diltiazem ; Calorimetry/methods ; Orosomucoid/metabolism ; Thermodynamics ; Drug Interactions
    Chemical Substances Warfarin (5Q7ZVV76EI) ; Clindamycin (3U02EL437C) ; Diltiazem (EE92BBP03H) ; Orosomucoid
    Language English
    Publishing date 2023-05-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24108472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Low-pressure chromatographic separation and UV/Vis spectrophotometric characterization of the native and desialylated human apo-transferrin

    Friganović, Tomislav / Tomašić, Antonela / Šeba, Tino / Biruš, Ivan / Kerep, Robert / Borko, Valentina / Šakić, Davor / Gabričević, Mario / Weitner, Tin

    Heliyon. 2021 Sept., v. 7, no. 9

    2021  

    Abstract: Low-pressure pH gradient ion exchange separation provides a fast, simple and cost-effective method for preparative purification of native and desialylated apo-transferrin. The method enables easy monitoring of the extent of the desialylation reaction and ...

    Abstract Low-pressure pH gradient ion exchange separation provides a fast, simple and cost-effective method for preparative purification of native and desialylated apo-transferrin. The method enables easy monitoring of the extent of the desialylation reaction and also the efficient separation and purification of protein fractions after desialylation. The N-glycan analysis shows that the modified desialylation protocol successfully reduces the content of the sialylated fractions relative to the native apo-transferrin. In the optimized protocol, the desialylation capacity is increased by 150 %, compared to the original protocol provided by the manufacturer. The molar absorption coefficients in the near-UV region for the native and desialylated apo-transferrin differ by several percent, suggesting a subtle dependence of the glycoprotein absorbance on the variable sialic acid content. The method can easily be modified for other glycoproteins and is particularly appropriate for quick testing of sialic acid content in the protein glycosylation patterns prior to further verification by mass spectrometry.
    Keywords absorbance ; absorption ; chromatography ; cost effectiveness ; glycoproteins ; glycosylation ; humans ; ion exchange ; mass spectrometry ; pH ; sialic acid ; ultraviolet radiation
    Language English
    Dates of publication 2021-09
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e08030
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Solvent effects on the absorption and fluorescence spectra of Zaleplon: Determination of ground and excited state dipole moments.

    Divac, Vera M / Šakić, Davor / Weitner, Tin / Gabričević, Mario

    Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy

    2019  Volume 212, Page(s) 356–362

    Abstract: Solvent effects on the absorption and fluorescence spectra of Zaleplon, a nonbenzodiazepine sedative/hypnotic drug that is mainly used for the short term treatment of insomnia, were investigated in 18 different solvents with diverse polarities. Dipole ... ...

    Abstract Solvent effects on the absorption and fluorescence spectra of Zaleplon, a nonbenzodiazepine sedative/hypnotic drug that is mainly used for the short term treatment of insomnia, were investigated in 18 different solvents with diverse polarities. Dipole moments of the ground and excited state (μ
    MeSH term(s) Absorption, Physicochemical ; Acetamides/chemistry ; Electrons ; Linear Models ; Pyrimidines/chemistry ; Quantum Theory ; Solvents/chemistry ; Spectrometry, Fluorescence
    Chemical Substances Acetamides ; Pyrimidines ; Solvents ; zaleplon (S62U433RMH)
    Language English
    Publishing date 2019-01-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 210413-1
    ISSN 1873-3557 ; 0370-8322 ; 0584-8539 ; 1386-1425
    ISSN (online) 1873-3557
    ISSN 0370-8322 ; 0584-8539 ; 1386-1425
    DOI 10.1016/j.saa.2019.01.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Low-pressure chromatographic separation and UV/Vis spectrophotometric characterization of the native and desialylated human apo-transferrin.

    Friganović, Tomislav / Tomašić, Antonela / Šeba, Tino / Biruš, Ivan / Kerep, Robert / Borko, Valentina / Šakić, Davor / Gabričević, Mario / Weitner, Tin

    Heliyon

    2021  Volume 7, Issue 9, Page(s) e08030

    Abstract: Low-pressure pH gradient ion exchange separation provides a fast, simple and cost-effective method for preparative purification of native and desialylated apo-transferrin. The method enables easy monitoring of the extent of the desialylation reaction and ...

    Abstract Low-pressure pH gradient ion exchange separation provides a fast, simple and cost-effective method for preparative purification of native and desialylated apo-transferrin. The method enables easy monitoring of the extent of the desialylation reaction and also the efficient separation and purification of protein fractions after desialylation. The
    Language English
    Publishing date 2021-09-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e08030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Hydrogen Isotope Exchange of Chlorinated Ethylenes in Aqueous Solution: Possibly a Termolecular Liquid Phase Reaction.

    Gabričević, Mario / Lente, Gábor / Fábián, István

    The journal of physical chemistry. A

    2015  Volume 119, Issue 51, Page(s) 12627–12634

    Abstract: This work reports an experimental study of the hydrogen/deuterium exchange in the basic aqueous solutions of trichloroethylene, trans-1,2-dichloroethylene, and cis-1,2-dichloroethylene using (1)H NMR as a monitoring method. 1,1-Dichlorethylene was also ... ...

    Abstract This work reports an experimental study of the hydrogen/deuterium exchange in the basic aqueous solutions of trichloroethylene, trans-1,2-dichloroethylene, and cis-1,2-dichloroethylene using (1)H NMR as a monitoring method. 1,1-Dichlorethylene was also investigated but found not to exchange hydrogen isotopes with water. The kinetics of isotope exchange features two different pathways, the first is first order with respect to hydroxide ion, whereas the second is second order. The first pathway is interpreted as a straightforward bimolecular reaction between chloroethylene and hydroxide ion, which leads to the deprotonation of chloroethylene. The second pathway involves a transition state with the association of one molecule of the chloroethylene and two hydroxide ions. It is shown that the second pathway could involve the formation of a precursor complex composed of one chloroethylene molecule and one hydroxide ion, but a direct termolecular elementary reaction is also feasible, which is shown by deriving a theoretical highest limit for the rate constants of termolecular reactions in solution.
    MeSH term(s) Deuterium Exchange Measurement ; Dichloroethylenes/chemistry ; Hydroxides/chemistry ; Kinetics ; Proton Magnetic Resonance Spectroscopy ; Solutions ; Stereoisomerism ; Trichloroethylene/chemistry ; Water/chemistry
    Chemical Substances Dichloroethylenes ; Hydroxides ; Solutions ; Water (059QF0KO0R) ; Trichloroethylene (290YE8AR51) ; hydroxide ion (9159UV381P) ; 1,2-dichloroethylene (XU9RUA6YUT)
    Language English
    Publishing date 2015-12-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1520-5215
    ISSN (online) 1520-5215
    DOI 10.1021/acs.jpca.5b10665
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  7. Article: Structural and electronic determinants of flavonoid binding to human serum albumin: an extensive ligand-based study

    Rimac, Hrvoje / Debeljak, Željko / Šakić, Davor / Weitner, Tin / Gabričević, Mario / Vrček, Valerije / Zorc, Branka / Bojić, Mirza

    RSC advances. 2016 Aug. 08, v. 6, no. 79

    2016  

    Abstract: Flavonoids are ubiquitous plant metabolites that interfere with different biological processes in the human organism. After absorption they bind to human serum albumin (HSA), the most abundant carrier protein in the blood which also binds various ... ...

    Abstract Flavonoids are ubiquitous plant metabolites that interfere with different biological processes in the human organism. After absorption they bind to human serum albumin (HSA), the most abundant carrier protein in the blood which also binds various hormones and drugs. Binding of flavonoids to HSA may impact their distribution, influencing the active concentration in the blood. To determine the most prominent features responsible for binding of 20 different flavonoid aglycones to the IIA region of HSA, in vitro fluorescence measurements and density functional theory (DFT) calculations were conducted. These results were then integrated to elucidate structure–affinity relationships. The presented results reveal that flavones and flavonoles bind most strongly to the IIA region of HSA. There are several electronic and structural determinants associated with flavonoid binding to this HSA region: high C3 nucleophilicity and partial charge of O4, high HOMO and LUMO energies, and coplanarity of AC and B rings. Both steric and electronic characteristics of flavonoids have a great impact on their binding to HSA, with hydrogen donor and acceptor properties and coplanarity being the most prominent.
    Keywords Lewis bases ; absorption ; blood ; density functional theory ; drugs ; flavones ; fluorescence ; hormones ; human serum albumin ; hydrogen ; metabolites
    Language English
    Dates of publication 2016-0808
    Size p. 75014-75022.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ISSN 2046-2069
    DOI 10.1039/c6ra17796d
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  8. Article ; Online: Genetic coding algorithm for sense and antisense peptide interactions.

    Štambuk, Nikola / Konjevoda, Paško / Turčić, Petra / Kövér, Katalin / Kujundžić, Renata Novak / Manojlović, Zoran / Gabričević, Mario

    Bio Systems

    2017  Volume 164, Page(s) 199–216

    Abstract: Sense and antisense peptides, i.e. peptides specified by complementary DNA and RNA sequences, interact with increased probability. Biro, Blalock, Mekler, Root-Bernstein and Siemion investigated the recognition rules of peptide-peptide interaction based ... ...

    Abstract Sense and antisense peptides, i.e. peptides specified by complementary DNA and RNA sequences, interact with increased probability. Biro, Blalock, Mekler, Root-Bernstein and Siemion investigated the recognition rules of peptide-peptide interaction based on the complementary coding of DNA and RNA sequences in 3'→5' and 5'→3' directions. After more than three decades of theoretical and experimental investigations, the efficiency of this approach to predict peptide-peptide binding has been experimentally verified for more than 50 ligand-receptor systems, and represents a promising field of research. The natural genetic coding algorithm for sense and antisense peptide interactions combines following elements: of amino acid physico-chemical properties, stereochemical interaction, and bidirectional transcription. The interplay of these factors influences the specificity of sense-antisense peptide interactions, and affects the selection and evolution of peptide ligand-receptor systems. Complementary mRNA codon-tRNA anticodon complexes, and recently discovered Carter-Wolfenden tRNA acceptor-stem code, provide the basis for the rational modeling of peptide interactions based on their hydrophobic and lipophilic amino acid physico-chemical properties. It is shown that the interactions of complementary amino acid pairs according to the hydrophobic and lipophilic properties strongly depend on the central (second) purine base of the mRNA codon and its pyrimidine complement of the tRNA anticodon. This enables the development of new algorithms for the analysis of structure, function and evolution of protein and nucleotide sequences that take into account the residue's tendency to leave water and enter a nonpolar condensed phase considering its mass, size and accessible surface area. The practical applications of the sense-antisense peptide modeling are illustrated using different interaction assay types based on: microscale thermophoresis (MST), tryptophan fluorescence spectroscopy (TFS), nuclear magnetic resonance spectroscopy (NMR), and magnetic particles enzyme immunoassay (MPEIA). Various binding events and circumstances were considered, e.g., in situations with-short antisense peptide ligand (MST), L- and D-enantiomer acceptors (TFS), in low affinity conditions (NMR), and with more than one antisense peptide targeting hormone (MPEIA).
    MeSH term(s) Algorithms ; Amino Acid Sequence/physiology ; Amino Acids/genetics ; Amino Acids/metabolism ; Animals ; Antisense Elements (Genetics)/genetics ; Antisense Elements (Genetics)/metabolism ; Genetic Code/physiology ; Humans ; Peptides/genetics ; Peptides/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
    Chemical Substances Amino Acids ; Antisense Elements (Genetics) ; Peptides ; RNA, Messenger
    Language English
    Publishing date 2017-10-28
    Publishing country Ireland
    Document type Journal Article ; Review
    ZDB-ID 186234-0
    ISSN 1872-8324 ; 0303-2647
    ISSN (online) 1872-8324
    ISSN 0303-2647
    DOI 10.1016/j.biosystems.2017.10.009
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  9. Article ; Online: Targeting Tumor Markers with Antisense Peptides: An Example of Human Prostate Specific Antigen.

    Štambuk, Nikola / Konjevoda, Paško / Turčić, Petra / Šošić, Hrvoje / Aralica, Gorana / Babić, Damir / Seiwerth, Sven / Kaštelan, Željko / Kujundžić, Renata Novak / Wardega, Piotr / Žutelija, Jelena Barać / Gračanin, Ana Gudelj / Gabričević, Mario

    International journal of molecular sciences

    2019  Volume 20, Issue 9

    Abstract: The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by ... ...

    Abstract The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2. the modeling of an antisense peptide (paratope) based on the epitope sequence, and 3. the spectroscopic evaluation of sense-antisense peptide binding. We then modified standard hPSA immunohistochemical staining practice by using a biotinylated antisense peptide instead of the standard monoclonal antibody and compared the results of both procedures. Immunochemical testing on human tissue showed the applicability of the antisense peptide technology to human molecular targets. This methodology represents a new approach to deriving peptide ligands and potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.
    MeSH term(s) Biomarkers, Tumor/immunology ; Humans ; Immunohistochemistry ; Male ; Nanomedicine/methods ; Peptides/immunology ; Prostate-Specific Antigen/immunology ; Prostatic Neoplasms/immunology ; Protein Structure, Secondary
    Chemical Substances Biomarkers, Tumor ; Peptides ; Prostate-Specific Antigen (EC 3.4.21.77)
    Language English
    Publishing date 2019-04-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20092090
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  10. Article ; Online: Modulation of γ2-MSH hepatoprotection by antisense peptides and melanocortin subtype 3 and 4 receptor antagonists.

    Turcic, Petra / Stambuk, Nikola / Konjevoda, Pasko / Kelava, Tomislav / Gabricevic, Mario / Stojkovic, Ranko / Aralica, Gorana

    Medicinal chemistry (Shariqah (United Arab Emirates))

    2014  Volume 11, Issue 3, Page(s) 286–295

    Abstract: Melanocortins, i.e., melanocyte stimulating hormones (MSH) are peptides with strong antiinflammatory effects. The most investigated aspects of γ2-MSH are related to cardiovascular effects and natriuresis, with limited research available about its anti- ... ...

    Abstract Melanocortins, i.e., melanocyte stimulating hormones (MSH) are peptides with strong antiinflammatory effects. The most investigated aspects of γ2-MSH are related to cardiovascular effects and natriuresis, with limited research available about its anti-inflammatory and cytoprotective effects. The aims of this study were: 1) to examine the effects of γ2-MSH and its derivative [D-Trp(8)]-γ2-MSH on the acetaminophen model of liver damage in CBA mice; 2) to evaluate the modulation of γ2-MSH hepatoprotection by melanocortin subtypes 3 and 4 receptor antagonists SHU 9119 and HS 024; 3) to define the importance of central MSH pharmacophore region (HFRW) by using antisense peptides LVKAT and VKAT. In this study, specific antagonists and antisense peptides were used to target central pharmacophore region of γ2-MSH and [D-Trp(8)]-γ2-MSH, enabling the evaluation of hepatoprotection from the standpoint of the receptor and pharmacophore blockade. The criteria for monitoring the effects of the hormones on the liver damage were alanine transaminase, aspartate transaminase activities (U/L), and pathohistological scoring of liver necrosis (scale 0-5). γ2-MSH (0.24 mg/kg) indicated hepatoprotective effects in comparison to control (p < 0.001). In contrast, [D-Trp(8)]-γ2-MSH did not show any hepatoprotective effects. Application of antagonists SHU 9119 and HS 024, and antisense peptides LVKAT and VKAT, also did not show any hepatoprotective effects. In fact, when combined with γ2-MSH, it annulled its hepatoprotective effect. The results provide evidence for hepatoprotective and antiinflammatory effects of the γ2-MSH in the liver.
    MeSH term(s) Acetaminophen ; Animals ; Chemical and Drug Induced Liver Injury/drug therapy ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Dose-Response Relationship, Drug ; Male ; Melanocyte-Stimulating Hormones/chemistry ; Melanocyte-Stimulating Hormones/pharmacology ; Mice ; Mice, Inbred CBA ; Oligonucleotides, Antisense/chemistry ; Oligonucleotides, Antisense/pharmacology ; Peptides, Cyclic/chemistry ; Peptides, Cyclic/pharmacology ; Receptor, Melanocortin, Type 3/antagonists & inhibitors ; Receptor, Melanocortin, Type 4/antagonists & inhibitors ; Structure-Activity Relationship
    Chemical Substances HS 024 ; Oligonucleotides, Antisense ; Peptides, Cyclic ; Receptor, Melanocortin, Type 3 ; Receptor, Melanocortin, Type 4 ; SHU 9119 (168482-23-3) ; Acetaminophen (362O9ITL9D) ; Melanocyte-Stimulating Hormones (9002-79-3)
    Language English
    Publishing date 2014-09-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1875-6638
    ISSN (online) 1875-6638
    DOI 10.2174/1573406410666140914161421
    Database MEDical Literature Analysis and Retrieval System OnLINE

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