Surface-modified nanospheres can be utilized for targeting drugs and diagnostic agents to the bone and bone marrow while extending their circulation time in the blood stream. The surface modification of poly(lactide-co-glycolide) (PLGA) nanospheres by radioisotope carrying poly(ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblock copolymers (Poloxamer 407) has been assessed by ...

The protein tyrosine phosphatase (PTP)-like phytase, PhyAsr, from Selenomonas ruminantium is a novel member of the PTP superfamily, and the only described member that hydrolyzes myo-inositol-1,2,3,4,5,6-hexakisphosphate. In addition to the unique substrate specificity of PhyAsr, the phosphate-binding loop (P-loop) has been reported to undergo a conformational change from an open (inactive) to a...

Analysis of mutations affecting the androgen receptor protein in human cells has been limited because of the low abundance and lability of these proteins in target tissues. All methods used to date have been based on the noncovalent interaction of radiolabeled androgens with the receptor's ligand binding site. We report here synthesis and use of the electrophilic affinity label dihydrotestoster...

Our constructed ligand efficiency (LE) hot spot surface was used as a guide for structure-based optimization of an AChBP fragment hit. This fragment hit was an analogue of a fragment found in the radioligand binding assay performed on Ls-AChBP, described in Chapter 4. The chemical space around this original fragment was explored by SAR-by-catalogue, thereby increasing its affinity and ligand ef...

For novel biotechnology-based termite control, we developed a cellulose bait containing freeze-dried genetically engineered yeast which expresses a protozoacidal lytic peptide attached to a protozoa-recognizing ligand. The yeast acts as a 'Trojan-Horse' that kills the cellulose-digesting protozoa in the termite gut, which leads to the death of termites, presumably due to inefficient cellulose d...

The physiological role played by protein-ligand recognition has motivated the development of several computational approaches to the ligand binding affinity. Some of them, termed rigorous, have a strong theoretical foundation but involve too much computation to be generally useful. Some others alleviate the computational burden by introducing strong approximations and/or empirical calibrations,...

Synapse-associated protein 102 (SAP102) and postsynaptic density-95 (PSD-95) bind to NMDA receptors through PDZ domains and cluster at excitatory postsynaptic sites called postsynaptic densities (PSD). We previously reported that PSD-95 containing mutated PDZ domains incapable of ligand binding clustered at synaptic sites with reduced efficiency. Here, we compared the synaptic clustering of the...

Identification of a tumor angiogenesis specific ligand would allow targeting of tumor vasculature. Lipidic vehicles can be used to deliver therapeutic agents for treatment of disease or contrast agents for molecular imaging. A targeting ligand would allow specific delivery of such formulations to angiogenic sites, thereby reducing side effects and gaining efficiency. Anginex, a synthetic 33-mer...

The synthesis, lanthanide complexation, and solvent extraction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counte...

Nanoparticle-mediated gene delivery is a promising alternative to viral methods; however, its use in vivo, particularly following systemic injection, has suffered from poor delivery efficiency. Although PEGylation of nanoparticles has been successfully demonstrated as a strategy to enhance colloidal stability, its success in improving delivery efficiency has been limited, largely due to reduced...