Two-dimensional fingerprints

4 Molecular Descriptors and Selection Techniques 13.4.1 Two-Dimensional Fingerprints 

MACCS substructure keys on the other hand encode the presence of a predefined set of relevant 2D fragments, originally designed for speeding up database substructure searching [48,49] by eliminating those compounds from detailed consideration that can- 

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Ni Y. Liu Y. Kokot S. Two-dimensional fingerprinting approach for comparison of complex substances analysed by HPLC-UV and fluorescence detection. Analyst, 2011,136 (3), 550-559. 

Radioiodination of nucleic acid (Fig. 7.22) is one of the earliest, convenient methods to obtain high specificity (Commerford, 1971) but its use has been declining considerably. It might still have some usefulness for in situ hybridization and, in the case of RNA, in two-dimensional fingerprint analysis. One should be aware of the volatile nature of I. The reaction is carried out in two stages (i) nucleic acid (10-1000 (xM as cytosine) is heated to 60°C for about 10 min in the presence of 30-100 p.M radioiodide, TICI3 at 5-10 times... 

Schuffenhauer A, Gillet VJ, Willett P. Similarity searching in files of three-dimensional chemical structures analysis of the BIOSTER database using two-dimensional fingerprints and molecular field descriptors. J Chem Inf Comput Sci 2000 40 295-307. 

Tan, L., Vogt, M., and Bajorath, J. 2009. Three-dimensional protein-ligand interaction scaling of two-dimensional fingerprints. Chem. Biol. Drug Des. 74 449-456. 

A further philosophical problem is that many of the descriptors used to date are derived from the field of similarity analysis, Two-dimensional fingerprints lose relevance once outside a defined structural family. It is an accepted fact that similarity values below about 0.5 are not reliable/significant. This is not a problem for clustering similar compounds, when one simply wants to know that compound A is not similar to compound B, but problems arise when it is important to know how dissimilar two compounds are. A pertinent critique of 2-D bit string descriptors has been presented by Flower. ... 

Figure 15.6 "Chemical space" plots illustrating the chemical diversity of a screening library. In the chemical space plots, each point represents a compound and the proximity of two points is indicative of the structural similarity (as defined by two-dimensional fingerprints and a Tanimoto index [69]) between the corresponding compounds. In (a) 13 hit series, in which active compounds were identified, are highlighted. Three of these are circled, corresponding to series 8,11, and 13, which are analyzed in more detail in Figure 15.7. The...

Qnadroni, M., et al., 1996. Analy.sis of global re.spon.ses by protein and peptide fingerprinting of protein.s i.solated by two-dimensional electrophore-.sis. Application to snlfate-starvation re.sponse of Escherichia coli. European Journal of Biochemistry 239 773-781. This paper de.scribes the n.se of tandem MS in the analysis of protein.s in cell extracts. 

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. 

Figure 15.10 presents the two-dimensional capillary electrophoresis fingerprint of a single MCF-7 breast cancer cell. This cellhad been fixed in 70% ethanol before analysis. 

Hu, S., Michels, D.A.,Fazal,M.A., Ratisoontom, C., Cunningham, M.L., Dovichi,NJ. (2004). Capillary sieving electrophoresis/micellarelectrokinetic capillary chromatography for two-dimensional protein fingerprinting of single mammalian cells. Anal. Chem. 76,4044-4049. 

C. Mello, E. Severi, L. Coelho, A. Marangoni, C. Dezuane, E. Ricci, D. Ribeiro and R.J. Poppi, Two-dimensional low resolution Raman spectroscopy applied to fast discrimination of microorganisms that cause pharyngitis a whole-organism fingerprinting approach, J. Mol. Struct, 883-884, 61-65 (2008). 

Two-dimensional electrophoresis [86] is a well established technique for the separation of intact proteins. In the first dimension the proteins are separated based on their isolectric point while the second dimension separates them based on their size. The presence on the gel of the proteins is revealed by Coomassie blue or silver staining. Under favorable conditions several thousand spots can be differentiated. The gel is digitized and computer-assisted analysis of the protein spot is performed. The spots of interest are excised either manually or automatically and then digested with trypsin. Trypsin cleaves proteins at the C-terminal side of lysine and arginine. In general one spot represents one protein and the peptides are analyzed by MALDI-TOF to obtain a peptide mass fingerprint. A peptide mass fingerprint involves the determination of the masses of all pep-... 

MDGC, and comprehensive two-dimensional GC, or GCxGC), faster separation techniques (fast GG), fast methods for quality assessment or process control in the flavour area ( electronic noses and fingerprinting MS) and on-line time-resolved methods for analysis of volatile organic compounds (VOGs) such as proton-transfer reaction MS (PTR-MS) and resonance-enhanced multi-photon ionisation coupled with time-of-flight MS (REMPI-TOFMS). The scope of this contribution does not allow for lengthy discussions on all available techniques therefore, only a selection of developments will be described. 

Fig. 15.14 Analytical techniques for time-resolved headspace analysis. An electronic nose can be used as a low-cost process-monitoring device, where chemical information is not mandatory. Electron impact ionisation mass spectrometry (EI-MS) adds sensitivity, speed and some chemical information. Yet, owing to the hard ionisation mode, most chemical information is lost. Proton-transfer-reaction MS (PTR-MS) is a sensitive one-dimensional method, which provides characteristic headspace profiles (detailed fingerprints) and chemical information. Finally, resonance-enhanced multiphoton ionisation (REMPI) TOFMS combines selective ionisation and mass separation and hence represents a two-dimensional method. (Adapted from [190])...

Fingerprinting. The characteristic two-dimensional paper chromatogram obtained from the partial hydrolysis of a protein or a nucleic acid. 

Fig. 17.3. The infected bile-ome Two-dimensional electrophoresis gel of F. hepatica infected host bile. Run on a 17 cm, pH 3-10, IPG strip in the first dimension and then on 12.5% SDS-PAGE gel in the second dimension with Coomassie blue staining. Host and parasite proteins were identified via their peptide mass fingerprints (Morphew, 2004, unpublished). Valid parasite secreted proteins can only come from in vivo proteomics.

Matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS) is now routinely used in many laboratories for the rapid and sensitive identification of proteins by peptide mass fingerprinting (PMF). We describe a simple protocol that can be performed in a standard biochemistry laboratory, whereby proteins separated by one- or two-dimensional gel electrophoresis can be identified at femtomole levels. The procedure involves excision of the spot or band from the gel, washing and de-stain-ing, reduction and alkylation, in-gel trypsin digestion, MALDI-TOF MS of the tryptic peptides, and database searching of the PMF data. Up to 96 protein samples can easily be manually processed at one time by this method. 

Schmidt, F., Schmid, M., Jungblut, P. R., Mattow, J., Facius, A., andPleissner, K. P. (2003) Iterative data analysis is the key for exhaustive analysis of peptide mass fingerprints from proteins separated by two-dimensional electrophoresis. J. Am. 

Arnott, D. P Henzel, W. J. Stults, J. T. 1995. Identification of proteins from two-dimensional electrophoresis gels by peptide mass fingerprinting. In Biochemical and Biotechnological Applications of Electrospray Ionization Mass Spectrometry, Snyder, A. E, ed., Washington, D.C. American Chemical Society, 619,226-243. 

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