Structure dereplication database

For this task, easily accessible properties of mixtures or pure metabolites are compared with literature data. This may be the biological activity spectrum against a variety of test organisms. Widely used also is the comparison of UV [90] or MS data and HPLC retention times with appropriate reference data collections, a method which needs only minimal amounts and affords reliable results. Finally, there are databases where substructures, NMR or UV data and a variety of other molecular descriptors can be searched using computers [91]. The most comprehensive data collection of natural compounds is the Dictionary of Natural Products (DNP) [92], which compiles metabolites from all natural sources, also from plants. More appropriate for dereplication of microbial products, however, is our own data collection (AntiBase [93]) that allows rapid identification using combined structural features and spectroscopic data, tools that are not available in the DNP. 

When a new impurity is encountered during chemical process research, retention time and molecular weight information are compared to the database for rapid identification. This approach is similar to the procedure described for natural product dereplication. If the compound is not contained in the structure database, then the corresponding LC/MS/MS analysis is performed to obtain substructural detail and the proposal of a new structure. 

Bradshaw et al. have disclosed a rapid and facile method for the dereplication of a purified natural product library [58]. The method integrates the molecular weight from low resolution MS data with the exact count of the number of methyl, methylene and methine groups obtained from ]H-13C NMR correlation data. Those structure properties were converted into a searchable text file that could be downloaded into a customized software program with chemical structure information in a specific format - SMILES. In the program, more than 120,000 unique structures were derived from commercial databases, such as Dictionary of Natural Products and Beilstein. 

Typically, dereplication is initiated with some analysis, chromatographic and/or spectroscopic, to recognise an active entity detected during HTS. Additional analyses are employed to rapidly establish the unambiguous identity of the compound. This fingerprint can then be used to search databases and reference libraries to link the structure to all chemical, spectral, bioactivity and pharmacokinetic data, as well as patent and publication information. 

There are numerous natural product databases that are used in dereplication such as Chemical Abstracts Service (CAS), Berdy s Bioactive Natural Products Database, Dictionary of Natural Products, MarinLit23 and AntiBase.24 Integration of structure-based and chemical shift searches, such as NAPROC-13,25 make these databases even more valuable. AntiMarin is a result of a recent merger between AntiBase and MarinLit 26 MarinLit and AntiMarin are the first commercially available databases that contain structural information (functional groups) as searchable fields.27... 

To illustrate how useful the unit-molecular-weight information is in natural product dereplication, Fig. 3A shows the unit-molecular-weight distribution of the approx 78,000 known natural products contained in the Chapman and Hall database (32). It can be seen that, for the reported natural products, determination of the molecular weight will narrow the reported structural possibilities to <800, and the largest number of known natural products that share a common unit molecular weight is only 759 (mol wt = 318). For that molecular weight, there are known natural products that exhibit 45 different empirical (or molecular) formulas, each of which adds up to approx 318 Dalton. 

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