DNA acidification by citric acid and gallic acid: acid binding site and DNA structural dynamics.

Communicated by Ramaswamy H. Sarma.

Application and biomolecular study of functionalized folic acid-dendrimer nanoparticles in drug delivery.

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.

Biomolecular study and conjugation of two para-aminobenzoic acid derivatives with serum proteins: drug binding efficacy and protein structural analysis.

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.

Binding efficacy of aminobenzoic acid derivatives with DNA duplex: drug binding sites and DNA structure and dynamics.

Communicated by Ramaswamy H. Sarma.

Locating the binding sites of citric acid and gallic acid on milk ß-lactoglobulin.

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.

Effect of tea catechins on tRNA structure and dynamics.

AbbreviationsCcatechinECGepicatechin gallateEGCGEpigallocatechin gallateAAdenineCcytosineGGuanineUuracilFTIRFourier transform infraredCommunicated by Ramaswamy H. Sarma.

Complexation of cis-Pt and trans-Pt(NH3)2Cl2 with serum proteins: A potential application for drug delivery.

AbbreviationsHAShuman serum albuminBSAbovine serum albuminß-LGbeta-lactoglobulincis-Pt and trans-PtPt(NH3)2Cl2FTIRFourier transform infraredCommunicated by Ramaswamy H. Sarma.

Conjugation of vitamin C with serum proteins: A potential application for vitamin delivery.

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-LG > HSA > 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.

Structural dynamics of DNA binding to tea catechins.

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 EGCG > ECG > 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 -4.59 kcal/mol (EGCG). Catechin conjugation induced major perturbations of DNA structure, while biopolymer remains in the B-family conformations.

Location of multiple binding sites for testo and testo-Pt(II) with tRNA.

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.