Active conformation relationship

Newman-Tancredi A, Cussac D, Marini L, Millan MJ. Antibody capture assay reveals bell-shaped concentration-response isotherms for h5-HTlA receptor-mediated G alpha(i3) activation conformational selection by high-efficacy agonists, and relationship to trafficking of receptor signaling. Mol Pharmacol 2002 62 590-601. 

Very fast electron transfers from P+ to bacteriochlorophyl (Bchl) and from (Bchl)- to QA do not depend on media dynamics and occur via conformationally non-equilibrium states (Fig.3.18). The dual fluorophore-nitroxide molecules (D-A) are also convenient objects for analysing the activity-dynamics relationship. The marked irreversible photoreduction of the nitroxide fragment of the dual probe incorporated into the binding site of HSA only took place when the nanosecond dynamical processes around the probe traced by ESR and fluorescence methods were detected (Rubtsova et al., 1993, Fogel et al, 1994 Likhtenshtein, 1986 Lozinsky et al., 2002). Similar results were reported for another model protein system, i.e. a-chymotrypsin with spin labeled methionin-92 groups (Belonogova et al., 1997). In the latter enzyme, the excited tryptophan group serves as an electron donor. 

A vastly different relationship between the active conformations of fentanyl and pethidine was deduced from a computer matching exercise carried out on these two analgesics (plus morphine) using the basic nitrogen center and three aromatic carbons as reference points.(mi Good matches were... 

Let Ca be the concentration of active conformation A the following relationships hold ... 

Under these circumstances, it is inevitable to estimate the active conformation of a chemical by another approach. The quantitative structure-activity relationship (QSAR) O) is one of the important approaches, particularly when the target site of a biologically active compound is unknown. Although X-ray crystallography is also helpful to estimate the active conformation, it provides the conformational information in a solid phase. More important is the conformation of a chemical in solution, which can be assigned in part by spectroscopic studies. Nuclear magnetic resonance (NMR) spectroscopy has been utilized to estimate the relative orientation of each atom in a molecule (2-5). Infra-red ( IR) spectroscopy is sometimes a useful tool, especially when hydrogen bonds are present ( ). Recently,... 

Taylor RE, Chen Y, Galvin GM, Prabba PK (2004) Conformation-activity relationships in polyketide natural products. Towards to biologically active conformation of epothilone. Org Biomol Chem 2 127-132... 

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