F

FDA see Food and Drug Administration fitness landscape 54, 57-58, 60-62, 64, 85 fitness value 57 flow cytometry 324 fluorescence signaling 246, 319 fluorescence intensity (FI) 314 fluorescence lifetime (FLT) 314 fluorescence polarization (FP) 314, 316 fluorescence resonance energy transfer (FRET) 303-304, 319 Food and Drug Administration (FDA) 363, 383-384, 405, 443, 446, 452 formulations 383 - polyalginate polylysine microparticles 386 FRET see fluorescence resonance energy transfer (FRET)...

Future Prospects for Aptamer Therapeutics

High-affinity aptamers can be generated readily against a variety of therapeutic protein targets, best illustrated perhaps, by the steady progression of aptamers selected against extracellular growth factors (VEGF, PDGF) and components of coagulation (thrombin, Factor IXa) and complement (C5) pathways through preclini-cal and clinical testing. With remarkable target specificity, versatile pharmaco-kinetic properties, ease of synthesis, and relatively low manufacturing costs, apta-mers are...

Conversion of Aptamers into Small Molecule Lead Compounds

Many pharmaceutical companies are primarily concerned with developing orally administered small-molecule drugs. This is because small-molecule drugs are inexpensive to produce and can potentially become blockbusters. Initially, compound libraries are screened in cell-based or biochemical assays to identify hits these are subsequently optimized in pharmaceutical hit-to-lead programs. Classical screening approaches are often supported by in silico methods to aid drug development. The ultimate...

Rationale for Targeting VEGF

Angiogenesis Foundation

Angiogenesis - the growth of new blood vessels - is a central component of many human disease processes (Witmer et al., 2003). There are several examples that have been areas of very active research. As solid tumors grow they require an ever-increasing supply of oxygen and nutrients, and hence develop their own vascular beds in order to meet this requirement. In patients with diabetes mellitus, chronically elevated blood glucose levels result in damage to small blood vessels and resultant...

Apical Loop Internal Loop Interactions

The presence of purine-purine pairs closing the loop of RNA hairpins giving rise to kissing complexes both in naturally interacting RNA species (the DIS element of HIV-1) and in selected RNA motifs (aptamers to TAR or to tRNAPhe) suggested that this might be a rule for generating stable loop-loop interactions. Indeed the substitution of a GC pair by a G,A combination at the top of the stem of the hairpin RNA I' stabilized its interaction with RNA II', two stem-loops derived from the structure...

Aptamers to Natural Products

Caffeine Aptamer Interaction With Target

Jenison et al. (1994) selected an RNA aptamer that binds to the alkaloid theophyl-line with high sensitivity and high specificity. Theophylline is used as bronchodi-lator in the treatment of asthma, bronchitis, and emphysema, but because of its narrow therapeutic index, serum levels must be monitored carefully to avoid serious poisoning. Theophylline is also chemically similar to theobromine and caffeine (Fig. 4.5), which may be present in serum samples due to consumption of coffee or...

Neuropeptide Calcitonin Generelated Peptide

Cerebral vessel vasodilation is a widely accepted hypothesis for the cause of migraine headaches. Neuro calcitonin gene-related peptide 1 (a-CGRP) induces vasodilation, and inhibition of this target may play a role in treating such headaches (Renfrey et al., 2003). Using a tailored-SELEX approach with an RNA-based library, 15 rounds of selection against rat a-CGRP were performed and a spiegelmer named STAR-F12 bound to a-CGRP with a Kd of 2.5 nmol L and inhibited a-CGRP-induced cAMP with an...