Activity fingerprinting

Figure 2.8 Compound biological activity biological activity fingerprints from 154...

Figure 2.14 BioPrint (partial) profile of some HMGCoA inhibitors. The two main structural classes are highlighted by a blue and purple box for both the activity fingerprint and the 2D structures.

The alkylation chemistry described above can also be appUed with fluorescein to yield the corresponding fluorescein mono-ethers such as 30 as green fluorescent probes for Upases [41]. These substrates are water soluble due to the anionic car-boxylate on the fluorescein group and can be used in pure aqueous buffer without any co-solvent This latter class of substrates reacts extremely fast and specificaUy with the enzymes, with assay times under 1 min. An activity fingerprinting study... 

Goddard, J.P. and Reymond, J.L (2004) Enzyme activity fingerprinting with substrate cocktails. Journal of the American Chemical Society, 126,11116 11117. 

Figure 10.10 Libraries of peptide-like structures containing warheads used to study the activity fingerprint of several proteases...

Considerable corrosion monitoring is carried out utilising invasive methods, i.e. where the corrosion sensor is required to penetrate the pipe or vessel wall. Avoidance of penetration using non-invasive methods (thin layer activation, ultrasonics, radiography and magnetic fingerprinting) is receiving considerable developmental attention. 

Since September 1997, the Journal of Chemical Education (JCE) publishes on a regular base a Classroom Activity that is set separately on a distinct hard sheet, including both the student activity (on one side) and instructor information sheet (on the back side). These activities are designed to actively engage students, while the topics covered are usually coimected with everyday life and apphcations (e.g. acid rain, bath bubblers, toothpastes, water filtration, anthocyanins, latent fingerprints, etc.). Liapi and Tsaparlis (2007) have used three of these activities (acid rain, bath bubblers, toothpastes) in conjunction with two conventional laboratory activities (some properties of acids/some properties of bases) with a class of ninth-grade students in Greece. An evaluation by the students showed a very positive result in favour of the JCE Activities they are connected with life and involve creativity on the part of the students (Fig. 5.2). 

Xue L, Stahura FL, Godden JW, Bajorath J. Mini-fingerprints detect similar activity of receptor ligands previously recognized only by three-dimensional pharmacophore-based methods. J Chem Inf Comp Sci 2001 41 394-401. 

Figure 3 Root fingerprints of Pseudomimets sp. associated with barley seedlings showing the production of siderophore by actively growing bacteria located in the zone of elongation behind the root tips. Root.s were pressed on to an iron-deficient minimal medium selective for Pseudomonas. After growth of the colonies, the production of siderophore was visualized by exposure of the agar plate to ultraviolet light, which causes the siderophore to Huoresce.

A second example of a VS exercise that was largely fingerprint-based was that of Boecker et al., in search of novel series for dopamine D2 and dopamine D3 blockers [65]. A set of known actives consisting of 472 dopamine D2 and D3 ligands was assembled from the literature. The SPECS database of 230,000 compounds was chosen from which to identify compounds. Two descriptor sets were calculated MOE2D [51] and CATS3D [77] for both query and database molecules. Neighbors... 

In addition to looking for data trends in physical property space using PCA and PLS, trends in chemical structure space can be delineated by viewing nonlinear maps (NLM) of two-dimensional structure descriptors such as Unity Fingerprints or topological atom pairs using tools such as Benchware DataMiner [42]. Two-dimensional NLM plots provide an overview of chemical structure space and biological activity/molecular properties are mapped in a 3rd and/or 4th dimension to look for trends in the dataset. 

The hormone itself can introduce complexity into bioassays. Many hormones must now be seen and understood not as chemical entities but as chemical pathways where hormonal activity is distributed across a number of chemical species. The more we learn about the pharmacological properties of members of a pathway, the more we are realizing that each one has a mix of common and unique properties. The practical point is that we must be careful about which hormone we choose to drive our bioassays. A hormonal chemical pathway may contain sinks as well as sources. Metabolism and uptake of a hormone can introduce significant distortions into bioassays. All of these factors leave their fingerprints on dose-response curves, and a pharmaceutical researcher developing a new bioassay has to learn to read the signs. 

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