RESUMO
Communicated by Ramaswamy H. Sarma.
Assuntos
Ácido Cítrico , Ácido Gálico , Sítios de Ligação , DNA/metabolismo , Concentração de Íons de Hidrogênio , Simulação de Dinâmica MolecularRESUMO
We determined the loading efficacy of folic acid - PAMAM - G3 and folic acid - PAMAM - G4 nanoparticles with doxorubicin (Dox), tamoxifen (Tam) and tetracycline (Tet) in aqueous solution at pH 7.2. Thermodynamic parameters ΔH0 -16 to -4 (kJ mol-1), ΔS0 31 to -0.3 (J mol-1K-1) and ΔG0 -14 to -11 (kJ mol-1) showed drug folic acid-PAMAM bindings are via ionic, H-bonding and van der Waals interactions. As acid - PAMAM size increased the stability and loading efficacy of drug-polymer conjugates were increased. The order of stability for drug-nanoparticles was doxorubicin > tetracycline > tamoxifen. TEM analysis showed major polymer morphological changes, upon drug encapsulation. Folic acid-PAMAM conjugates are effective drug delivery tools in vitro. Communicated by Ramaswamy H. Sarma.
Assuntos
Dendrímeros , Nanopartículas , Preparações Farmacêuticas , Doxorrubicina , Sistemas de Liberação de Medicamentos , Ácido FólicoRESUMO
Communicated by Ramaswamy H. Sarma.
Assuntos
Simulação de Dinâmica Molecular , Preparações Farmacêuticas , Sítios de Ligação , DNA , Simulação de Acoplamento MolecularRESUMO
ß-Lactoglobulin (ß-LG) is a member of lipocalin superfamily of transporters for small hydrophobic and hydrophilic molecules. We located the binding sites of citric acid and gallic acid on ß-lactoglobulin (ß-LG) in aqueous solution at physiological conditions, using spectroscopic methods, thermodynamic analysis and molecular modeling. Thermodynamic parameters ΔH0 -9.5 to -6.9 (kJ mol-1), ΔS0 23.9 to 13.6 (J mol-1K-1) and ΔG0 -14.5 to -13.6 (kJ mol-1) showed that acid binds protein via ionic contacts with gallic acid forming stronger protein conjugates consistent with theoretical modeling. Different amino acids are involved in gallic acid and citric acid complexation. Protein conformation was altered with reduction of ß-sheet from 58% (free protein) to 46-43% and a major increase in α-helix from 11% (free protein) to 29-23% and random coil structure in the acid-protein, indicating a partial protein destabilization. Communicated by Ramaswamy H. Sarma.
Assuntos
Lactoglobulinas , Leite , Animais , Sítios de Ligação , Ácido Cítrico , Ácido Gálico , Lactoglobulinas/metabolismo , Ligação Proteica , TermodinâmicaRESUMO
Two aminobenzoic acid derivatives DAB-0 and DAB-1 showed distinct biological properties on murine bladder cancer (BCa) cell line MB49-I. In contrast to DAB-1, DAB-0 does not possess any anti-inflammatory activity and is less toxic. Furthermore, DAB-0 does not interfere with INFγ-induced STAT1 activation and TNFα-induced IκB phosphorylation, while DAB-1 does. In order to rationalize these results, the binding efficacy of DAB-0 and DAB-1 with serum proteins such a human serum albumin (HSA), bovine serum albumin (BSA) and beta-lactoglobulin (ß-LG) was investigated in aqueous solution at physiological pH. Multiple spectroscopic methods and thermodynamic analysis were used to determine the binding efficacy of DAB-0 and DAB-1 with serum proteins. Drug-protein conjugation was observed via through ionic contacts. DAB-1 forms stronger adducts than DAB-0, while ß-LG shows more affinity with the order of stability ß-LG > BSA > HSA. The stronger complexation of DAB-1 with serum proteins might account for its biological potential and transport in the blood. The binding efficacy ranged from 40 to 60%. Major alterations of protein secondary structures were detected upon drug complexation. Serum proteins are capable of delivering DAB-1 in vitro.Communicated by Ramaswamy H. Sarma.
Assuntos
Ácido 4-Aminobenzoico , Preparações Farmacêuticas , Animais , Humanos , Lactoglobulinas/metabolismo , Camundongos , Ligação Proteica , Soroalbumina Bovina/metabolismo , Albumina Sérica HumanaRESUMO
AbbreviationsHAShuman serum albuminBSAbovine serum albuminß-LGbeta-lactoglobulincis-Pt and trans-PtPt(NH3)2Cl2FTIRFourier transform infraredCommunicated by Ramaswamy H. Sarma.
Assuntos
Proteínas Sanguíneas , Cisplatino , Sistemas de Liberação de MedicamentosRESUMO
AbbreviationsCcatechinECGepicatechin gallateEGCGEpigallocatechin gallateAAdenineCcytosineGGuanineUuracilFTIRFourier transform infraredCommunicated by Ramaswamy H. Sarma.
Assuntos
Catequina/química , Catequina/farmacologia , Conformação de Ácido Nucleico/efeitos dos fármacos , RNA de Transferência/química , Chá/química , Humanos , Estrutura Molecular , Análise Espectral , Relação Estrutura-Atividade , TermodinâmicaRESUMO
Vitamin C plays an important role in human health and therefore, the bioavailability and delivery of this micronutrient in solution have been the subject of intensive studies. Serum proteins are known to play an important role as drug delivery tools with important clinical applications. The conjugation of l-ascorbic acid with human serum albumin (HSA), bovine serum albumin (BSA) and beta-lactoglobulin (ß-LG) was investigated in aqueous solution at physiological pH. Multiple spectroscopic methods, thermodynamic analysis and modeling were used to determine the binding efficacy of the vitamin C with serum proteins. Acid-protein conjugation occurred via ionic contacts. Acid forms more stable adducts with ß-LG with the order of stability ß-LGâ¯>â¯HSAâ¯>â¯BSA. The loading efficacy was 45-60%. Major alterations of protein secondary structures were observed upon acid conjugation. Serum proteins can deliver vitamin C in vitro.
Assuntos
Ácido Ascórbico/química , Proteínas Sanguíneas/química , Portadores de Fármacos/química , Animais , Humanos , Modelos Moleculares , Conformação Proteica , TermodinâmicaAssuntos
Doxorrubicina/química , Portadores de Fármacos/química , Nanopartículas/química , Tamoxifeno/química , Tetraciclinas/química , Quitosana/química , Doxorrubicina/administração & dosagem , Ácido Fólico/química , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Tamoxifeno/administração & dosagem , Tetraciclinas/administração & dosagem , TermodinâmicaRESUMO
We determined the conjugation and binding efficacy of tea catechins (+)-catechin (C), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) with calf thymus DNA in aqueous solution at physiological pH. Thermodynamic analysis showed that tea catechins bind DNA via hydrophilic and hydrophobic interactions with the binding efficacy of 45-60%. Larger catechins form more stable DNA adducts with the order of stability EGCGâ¯>â¯ECGâ¯>â¯C. Modeling showed catechin-DNA conjugation occurs via both G-C and A-T base pairs with the free binding energy of -4.46 (C), -4.51 (EGC) and -4.59â¯kcal/mol (EGCG). Catechin conjugation induced major perturbations of DNA structure, while biopolymer remains in the B-family conformations.
Assuntos
Catequina/química , DNA/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Chá/química , Conformação Molecular , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade , Análise Espectral , TermodinâmicaRESUMO
We report the binding of testo and testo-Pt(II) complexes (testosterone derivatives) with tRNA in aqueous solution at physiological pH. Thermodynamic parameter ΔH0 -8 to -3 (kJ mol-1), ΔS0 35 to 18 (J mol-1K-1) and ΔG0 -14 to -13 (kJ mol-1) and other spectroscopic results showed drug-tRNA binding occurs via ionic contacts with testo-Pt(II) forming more stable tRNA complexes in comparison to testo: Ktesto-Pt(II)-tRNA= 3.2 (± 0.9) × 105 M-1 > Ktesto-tRNA= 2.1 (± 0.7) × 105 M-1. Molecular modeling showed multiple binding sites for testo and testo-Pt(II) on tRNA molecule. Some of the useful molecular descriptors are calculated. Major structural changes were observed for biopolymers upon drug complexation, while tRNA remains in the A-family structures.
Assuntos
Antineoplásicos/química , RNA de Transferência/química , Testosterona/análogos & derivados , Antineoplásicos/farmacologia , Sítios de Ligação , Concentração de Íons de Hidrogênio , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico/efeitos dos fármacos , Compostos Organoplatínicos , RNA de Transferência/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Testosterona/química , TermodinâmicaRESUMO
The development of new targeted anticancer agents able to efficiently and specifically destroy cancer cells with minimal toxic side effects is nowadays a subject of intensive research endeavors. We report the conjugation of testo and testo-Pt(II) (two semi-synthetic testosterone derivatives) with calf thymus DNA in aqueous solution at physiological pH. Multiple spectroscopic methods, thermodynamic analysis and modeling were used to determine the binding efficacy of these drugs to DNA duplex. Thermodynamic parameters showed drug-DNA conjugation occurs via ionic interactions with testo-Pt(II) forming more stable DNA adducts than testo with Ktesto-DNAâ¯=â¯1.80 (±0.5) x 105â¯M-1 and Ktesto-Pt(II)-DNAâ¯=â¯2.3 (±0.8) x 105â¯M-1. Molecular modeling shows that testo and testo-Pt(II) bind DNA at different locations.
Assuntos
Antineoplásicos/química , DNA/química , Compostos Organometálicos/química , Platina/química , Testosterona/química , Animais , Antineoplásicos/síntese química , Bovinos , Concentração de Íons de Hidrogênio , Modelos Moleculares , Compostos Organometálicos/síntese química , TermodinâmicaRESUMO
The potential application of hybrid anticancer molecules requires further investigation. There is a great interest in developing new site-specific anticancer agents able to efficiently destroy cancer cells with minimal toxic side effects. Serum proteins are known to play an important role as drug delivery system with important clinical applications. Hence, the conjugation of testo and testo-Pt(II) (two semi-synthetic testosterone derivatives) with human serum albumin HSA), bovine serum albumin (BSA) and beta-lactoglobulin (ß-LG) was investigated in aqueous solution at physiological pH. Multiple spectroscopic methods, thermodynamic analysis and modeling were used to determine the binding efficacy of these bioactive compounds to serum proteins. Drug-protein conjugation occurred via ionic contacts. BSA forms more stable conjugates than HSA and ß-LG with the order of stability testoâ¯>â¯testo-Pt(II). Major alterations of protein secondary structures were observed upon drug complexation. Serum proteins can be used to deliver these bioactive materials in vitro.
Assuntos
Lactoglobulinas/química , Platina/química , Soroalbumina Bovina/química , Albumina Sérica Humana/química , Testosterona/química , Animais , Bovinos , Humanos , Estrutura Secundária de ProteínaRESUMO
It has been shown that encapsulation of dietary polyphenols leads to increased solubility and bioavailability of these micronutrients. The encapsulation of dietary polyphenols resveratrol, genistein, and curcumin by folic acid-PAMAM-G3 and folic acid-PAMAM-G4 nanoparticles was studied in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images, and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic, and H-bonding contacts with resveratrol forming more stable conjugates. As folic acid-PAMAM nanoparticle size increased, the loading efficacy and the stability of polyphenol-polymer conjugates were increased. Polyphenol encapsulation induced major alterations of dendrimer morphology. Folic acid-PAMAM nanoconjugates are capable of delivery of polyphenols in vitro.
Assuntos
Curcumina/química , Dendrímeros/química , Ácido Fólico/química , Genisteína/química , Micronutrientes/química , Nanocápsulas/química , Nylons/químicaRESUMO
Functionalized folic-polymers were often used for gene and drug delivery. DNA binding to folic acid-PAMAM conjugates was studied, using multiple spectroscopic methods, thermodynamic analysis and transmission electron microscopy (TEM). Thermodynamic parameters showed DNA-folic acid-PAMAM conjugation occurs via H-bonding, hydrophobic and van der Waals contacts. As nanoparticle size increases the loading efficacy and the stability of DNA conjugates are enhanced. TEM analysis showed major DNA morphological changes, upon folic acid-PAMAM conjugation. Folic acid-PAMAM nanoparticles can transport DNA in vitro.
Assuntos
DNA/metabolismo , Dendrímeros/química , Ácido Fólico/química , Nanopartículas/metabolismo , DNA/química , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Tamanho da Partícula , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , TermodinâmicaRESUMO
tRNA binding efficacy to folic acid-PAMAM nanoparticles was determined, using multiple spectroscopic methods, thermodynamic analysis and transmission electron microscopy (TEM). The structural analysis showed tRNA binds folic acid-PAMAM through H-bonding, hydrophobic and van der Waals contacts. As PAMAM size increases the binding efficacy and the stability of tRNA conjugates are enhanced. TEM analysis showed major tRNA morphological changes, upon folic acid-PAMAM complexation. Folic acid-PAMAM nanoparticles can transport tRNA in vitro.
Assuntos
Dendrímeros/metabolismo , Portadores de Fármacos/metabolismo , Ácido Fólico/metabolismo , Nanoconjugados , Nylons/metabolismo , RNA de Transferência/metabolismo , Sistemas de Liberação de Medicamentos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica , Nanoconjugados/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaAssuntos
Quitosana/metabolismo , DNA/metabolismo , Ácido Fólico/metabolismo , Nanoconjugados/química , Animais , Bovinos , Quitosana/química , DNA/ultraestrutura , Ácido Fólico/química , Cinética , Nanoconjugados/ultraestrutura , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
We report the loading efficacy of folic acid (FA) by polyamidoamine (PAMAM-G3 and PAMAM-G4) nanoparticles in aqueous solution at physiological pH. Thermodynamic parameters ΔH = -47.57 (kJ Mol-1), ΔS = -122.78 (J Mol-1, K-1) and ΔG = -10.96 (kJ Mol-1) showed FA-PAMAM bindings occur via H-bonding and van der Waals contacts. The stability of acid-PAMAM conjugate increased as polymer size increased. The acid loading efficacy was 40 to 50%. TEM images exhibited major polymer morphological changes upon acid encapsulation. PAMAM dendrimers are capable of FA delivery in vitro.
Assuntos
Dendrímeros/química , Ácido Fólico/química , Poliaminas/química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão/métodos , Nanopartículas/química , Nylons/química , Tamanho da Partícula , Polímeros/química , Espectrofotometria Ultravioleta/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , TermodinâmicaRESUMO
Dietary polyphenols are abundant micronutrients in our diet and paly major role in prevention of degenerative diseases. The binding efficacy of antioxidant polyphenols resveratrol, genistein, and curcumin with PAMAM-G3 and PAMAM-G4 nanoparticles was investigated in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images, and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic, and H-bonding contacts with resveratrol forming more stable conjugates. As PAMAM size increased the loading efficacy and the stability of polyphenol-polymer conjugates were increased. Polyphenol binding induced major alterations of dendrimer morphology. PAMAM nanoparticles are capable of delivery of polyphenols in vitro.
Assuntos
Antioxidantes/química , Dendrímeros/química , Portadores de Fármacos/química , Nanopartículas/química , Nylons/química , Polifenóis/química , Curcumina/química , Genisteína/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Simulação de Acoplamento Molecular , Resveratrol/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The conjugation of tRNA with folic acid-chitosan conjugates was studied, using multiple spectroscopic methods and transmission electron microscopy (TEM). Thermodynamic analysis ΔH -14 to -10 (KJMol-1) and ΔS 14 to -1 (JMol-1, K-1) showed tRNA-folic acid-chitosan bindings occur via H-bonding, hydrophobic and van der Waals contacts. The loading efficacy and the stability of tRNA conjugates were enhanced as folic acid-chitosan size increased. TEM analysis showed major tRNA morphological changes, upon folic acid-chitosan conjugation. No alteration of tRNA conformation was observed on conjugate formation. Folic acid-chitosan conjugates can deliver tRNA in vitro.