Endogenous small molecules

Estimation of the glomerular filtration rate (GFR) is considered a sensitive index of functional nephron mass (Newman and Price 1999). Point measurements of the plasma levels of several endogenous small molecules (urea, creatinine, 2-(a-mannopyranosyl)-L-tryptophan) or small (less than 66 kDa) proteins (cystatin C (y-trace), prostaglandin D synthase (15-trace protein), ai-microglobulin, p2-microglobulin, and retinol binding protein) have been used to assess GFR in many species. 

Pharmacophores usually address the tightly confined environments of enzyme active sites or protein binding sites for endogenous small molecule ligands. Their limited size means that they are prone to recognizing the active sites of proteins related to their actual target because they have insufficient reach to discriminate... 

Endogenous small molecules such as phosphoserine and ATRA were also found to promote neural differentiation. Although ATRA has been shown to promote neurogenesis in vivo it shows relatively low levels of efficiency in vitro, and is also unstable upon irradiation. In an attempt to circumvent this problem, Christie et al. prepared stable ATRA mimics based on biaryl acetylenes. Intriguingly, /jara-substituted 4a was observed to give rise to a neural phenotype in vitro, but the corresponding meta-isomer 4b was observed to give primarily epithelial phenotype upon treatment of the same precursor cells. 

AppHcation of this strategy to other members of the hormone receptor superfamily would appear possible. The homology of the hormone receptor superfamUy has been well studied, and endogenous small molecule Hgands have been identified for most Examples include the progesterone and vitamin... 

Viral infections continue to be significant causes of morbidity and mortality and at the same time continue to be resistant to treatment by small molecules. Avridine (6) is an antiviral compound which has shown some activity in a variety of animal tests apparently based upon its ability to stimulate a number of cells to produce the high molecular weight endogenous antiviral substance interferon. Thus, the compound is believed to operate indirectly by stimulating the body s own natural defenses against viral penetration into host cells. Avridine is synthesized by... 

In the absence of an endogenous centre, the specificity of relaxation data can be improved by introducing in known positions paramagnetic probes. The unpaired electron spin enhances the relaxation rate of the surrounding nuclei in a distance-dependent fashion. In this way, it is possible to evaluate specific interaction sites between a marked polymer and the small molecules. 

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

The endogenous hormone atrial natriuretic peptide (ANP), which acts to increase blood pressure, is, like many other effector peptides, excised from a longer native chain by an endopeptidase enzyme, that is, an agent that cleaves bonds well along the chain of amino acids. A small-molecule endopeptidase inhibitor lowers blood pressure by inhibiting the release of ANP. The inhibitor candoxatril (6-8) is now... 

Landsteiner in 1930s found that small molecules could stimulate an immune reaction if combined with a protein. This finding that small molecules could be recognized by the immune system if attached to a larger molecule such as an endogenous protein became the hapten hypothesis. 

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