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Biomedical subjects

Nicholas O Fischer

Publications and source records attributed to Nicholas O Fischer.

5 recordsLinked to original sources
PubMed2006

Dual-acting agents that possess free radical scavenging and antithrombotic activities: design, synthesis, and evaluation of phenolic tetrahydro-beta-carboline RGD peptide conjugates.

A new approach to construct a single dual-acting agent is described. Compounds 6a-c are potent free radical scavengers as demonstrated by the EC(50) values in PC12 cell survival assay in term of NO, H(2)O(2), and ()OH scavenging activity. The Ach-induced vaso-relaxation assay further confirms the potent NO scavenging activity of compounds 6a-c. In addition, 6a-c are efficacious in a rat arterial thrombosis, and are active in ADP- or PAF-induced in vitro platelet aggregation assay, suggesting that compounds 6a-c also possess anti-thrombotic activities. Since both free radical and thrombogenesis are important risk factors in myocardial ischemic/reperfusion injuries, these dual-acting agents having both free radical scavenging and antithrombolic activities may potentially be beneficial toward their treatment.

Adenosine Diphosphate↗
PubMed2004

Control of protein structure and function through surface recognition by tailored nanoparticle scaffolds.

Thioalkyl and thioalkylated oligo(ethylene glycol) (OEG) ligands with chain-end functionality were used to fabricate water-soluble CdSe nanoparticle scaffolds. Surface recognition of chymotrypsin (ChT) was achieved using these functionalized nanoparticle scaffolds, with three levels of interaction demonstrated: no interaction (OEG terminated with hydroxyl group), inhibition with denaturation (carboxylate-terminated thioalkyl ligands), and inhibition with retention of structure (carboxylate-terminated OEG). The latter process was reversible upon an increase in ionic strength, with essentially complete restoration of enzymatic activity.

Cadmium Compounds↗
PubMed2003

Reversible "irreversible" inhibition of chymotrypsin using nanoparticle receptors.

Anionically functionalized amphiphilic nanoparticles efficiently inhibit chymotrypsin through electrostatic binding followed by protein denaturation. We demonstrate the ability to disrupt this "irreversible" inhibition of chymotrypsin through modification of the nanoparticle surface using cationic surfactants. Up to 50% of original chymotrypsin activity is rescued upon long-chain surfactant addition. Dynamic light-scattering studies demonstrate that chymotrypsin is released from the nanoparticle surface. The conformation of the rescued chymotrypsin was characterized by fluorescence and fluorescence anisotropy, indicating that chymotrypsin regains a high degree of native structure upon surfactant addition.

Carboxylic Acids↗
PubMed2002

Inhibition of chymotrypsin through surface binding using nanoparticle-based receptors.

Efficient binding of biomacromolecular surfaces by synthetic systems requires the effective presentation of complementary elements over large surface areas. We demonstrate here the use of mixed monolayer protected gold clusters (MMPCs) as scaffolds for the binding and inhibition of chymotrypsin. In these studies anionically functionalized amphiphilic MMPCs were shown to inhibit chymotrypsin through a two-stage mechanism featuring fast reversible inhibition followed by a slower irreversible process. This interaction is very efficient, with a K(i)(app) = 10.4 +/- 1.3 nM. The MMPC-protein complex was characterized by CD, demonstrating an almost complete denaturation of the enzyme over time. Dynamic light scattering studies confirm that inhibition proceeds without substantial MMPC aggregation. The electrostatic nature of the engineered interactions provides a level of selectivity: little or no inhibition of function was observed with elastase, beta-galactosidase, or cellular retinoic acid binding protein.

Anions↗