Activity profiling

J, P Willett and ] Bradshaw 1998. Identification Of Biological Activity Profiles Using Sub- tural Analysis And Genetic Algorithms. Journal of Chemical Information and Computer Science 55-179. 

The PGs, PGI2 and TXA2 collectively exhibit a wide variety of biochemical and pharmacological activities and are iavolved ia both physiological and pathophysiological processes. However, the iadividual compounds show different overall activity profiles sometimes ia opposiag directions. Excellent reviews are available (59—64). A survey of some of the more important biological actions of the prostanoids foUow. 

The stmctures of selected cephalosporins on the U.S. market, or in the final stages of development, are shown in Tables 4—8 (see also 78, 87). For every cephalosporin which has made it to the marketplace, HteraHy thousands of analogues were synthesized in order to estabUsh the stmcture-activity profile and allow selection of a clinical candidate. In addition to these compounds, there is a tremendous number of cephalosporin compounds currendy at various stages of development. A more extensive listing of the newer cephalosporins under preclinical or clinical evaluation may be found in a number of reviews (79,88). 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

FIGURE 14.11 The pH activity profiles of four different enzymes. Trypsin, an intestinal protease, has a slightly alkaline pH optimnm, whereas pepsin, a gastric protease, acts in the acidic confines of the stomach and has a pH optimmn near 2. Papain, a protease found in papaya, is relatively insensitive to pHs between 4 and 8. Cholinesterase activity is pH-sensitive below pH 7 but not between pH 7 and 10. The cholinesterase pH activity profile suggests that an ionizable group with a pK near 6 is essential to its activity. Might it be a histidine residue within the active site ... 

Very recently, the Shipman group have made a further step towards a comprehensive structure/activity profile for noncovalent interactions between azinomycin B and DNA [152]. They synthesized simplified azinomycin analogues 69 and 96-98 (Scheme 11.13), retaining both the epoxide and aziridine alkylating functionalities, with systematically altered substitution on the naphthoate fragment, and analyzed their DNA crosslinking by gel electrophoresis. They found that cross-... 

Krieger, N., and Hastings, J. W. (1968). Bioluminescence pH activity profiles of related luciferase fractions. Science 161 586-589. 

A gene activity profile is a collection of quantitatively determined levels of gene products, found in one tissue or cell type, which is characteristic of the tissue, a disease process, a hormone response, a pharmaceutical intervention, etc. 

CmC, a preservative in commercial preparations of some intravenous drugs, activates CICR in a way similar to that of caffeine. 4-CmC is more potent than caffeine and shows isoform-dependent activation profiles it is much less effective in RyR3 than RyRl or RyR2. 

Gene Activity Profile Gene Array Gene Chip... 

Figure 2.42. Relative steady-state methanation activity profiles for Ni ( ), Co (A), Fe ( ), and Ru (O) as a function of gas-phase H2S concentration. Reaction conditions 100 kPa, 400°C, 1% CO/99%H2 for Co, Fe, and Ru, 4% CO/96% H2 for Ni.131 Reprinted with permission from Academic Press.

Garrett NE, Stack HE, Waters MD. 1986. Evaluation of the genetic activity profiles of 65 pesticides. MutatRes 168 301-326. 

The importance of solvation on reaction surfaces is evident in striking medium dependence of reaction rates, particularly for polar reactions, and in variations of product distributions as for methyl formate discussed above and of relative reactivities (18,26). Thus, in order to obtain a molecular level understanding of the influence of solvation on the energetics and courses of reactions, we have carried out statistical mechanics simulations that have yielded free energy of activation profiles (30) for several organic reactions in solution (11.18.19.31. ... 

Fliri AF, Loging WT, Thadeio PF, Volkmann RA. Biological spectra analysis Linking biological activity profiles to molecular structure. Proc Natl Acad Sci USA 2005 102 261-6. 

Activity profiles of Ti02-suppoited metal Fig. 2. Co 2p XPS spectra of 5 wt.% CoOx/TiOa for catalytic wet TCE oxidation 310 K. and reference Co chemicals, (a) fresh (b) spent. 

Fig. 2. Activity profiles of ethylene polymerization (a) with homogenous catalyst ...

Figure 17.9 Schematic representation of the proposed activity profile of an ideal neuroleptic. The figure shows DA pathways to the prefrontal cortex, mesolimbic nucleus accumbens and striatum the effects required for an ideal drug on the DA influence and symptoms there and to what extent they are met by most typical and atypical neuroleptics and by clozapine. Note that while all atypical neuroleptics induce few extrapyramidal w side-effects (EPSs) few of them, apart from clozapine, have much beneficial effect in overcoming negative symptoms of schizophrenia ...

Figure 5. pH activity profile of PGE on polygalacturonate. Mcllvaine buffers were used in the pH range from 2.5 to 5,5, Reducing sugars were detected by the neocuproine method. PGE (2 mg/ml) was 80-times diluted and incubated with 500 pi of a 0.25% (w/v) polygalacturonate solution, at SO C. 

Suomalainen, P., Johans, G., Soderlund, T., Kinnunen, P. K. Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability. J. Med. Chem. 2004, 47, 1783-1788. 

P. J. Lewi, Spectral mapping, a technique for classifying biological activity profiles of chemical compounds. Arzneim. Forsch. (Drug Res.), 26 (1976) 1295-1300. 

Loeomotor aetivity has historically been used as an index of psychostimulant effects. Simple assessment of amount of loeomotor activity can provide the basis for anatomical as well as pharmaeologieal analysis of the neural substrates that mediate the behavioral expression of stimulant action. More sophisticated behavioral measurement systems ean reeord multiple measures of activity and describe spatial and temporal patterning of loeomo-tion. In such systems, qualitative aspects of behavioral activation can be evaluated by examining the entire activity profile. A comparison of the effects of novel drugs with those produced by well-characterized substanees may lead to a better understanding of their mechanisms of action and subjective properties. 

MDMA significantly altered the behavioral activity profile of rats. 

Because mixing consists of many small events which progressively move the sediment grains it is akin to diffusion and can be modeled as such following the mathematical approach of Guinasso and Schink (1975). °Pb and " Th decay as they are mixed downwards which leads to an activity profile in the sediment which decreases exponentially with depth (Fig. 12). The activity of the nuclide, A, is given by (Anderson et al. 1988) ... 

Figure 3 shows the final chromatogram and activity profile of purified alpha-endopsychosin. The first peak contained most of the PCP displacing activity as measured by its ability to inhibit 3H-PCP. An aliquot of the most active material was hydrolyzed in acid and the amino acid composition was determined using OPA detection. It was determined that the peptide contained approximately 26 amino acids, in close agreement with the molecular weight predicted by Sephadex gel filtration studies. N-terminal analysis revealed that the peptide was blocked at this site. The nature of this blockade is yet to be determined. Studies are under way to determine the amino acid sequence of the peptide. 

Panel B Activity profiles of bombesin, neuropeptide Y, and substance p from the same HPLC fractions. 

The antimicrobial activity profile is as such it acts very quickly and in some products this is used to a positive effect as it enables an antibacterial claim to be achieved for face cleansing and purifying products. 

There are two catalytically active residues in pepsin Asp-32 and Asp-215. Their ionizations are seen in the pH-activity profile, which has an optimum at pH 2 to 3, and which depends upon the acidic form of a group of pKa 4.5 and the basic form of a group of pKa 1.1.160,161 The pKa values have been assigned from the reactions of irreversible inhibitors that are designed to react specifically with ionized or un-ionized carboxyl groups. Diazo compounds—such as A-diazoacetyl-L-phenylalanine methyl ester, which reacts with un-ionized carboxyls—react specifically with Asp-215 up to pH 5 or so (equation 16.28).162-164 Epoxides, which react specifically with ionized carboxyls, modify Asp-32 (equation 16.29). 

Plant physiologists and other biological scientists also have their important role to play in allelopathy. They must devise suitable bioassays to detect the suspected allelopathic compounds, follow the biological activity of the individual and associated chemicals, develop activity profiles for identified chemicals, and determine the conditions (dose/response) for chemicals to arrive at the threshold levels. They must also determine which chemicals contribute... 

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