Markush technique

Key words Virtual combinatorial library, Markush technique, compound analysis, chemoinfor-... 

Barnard, J.M., Downs, G.M., ScHOLLEY-PFAB, A.V., and Brown, R. D. Use of Markush structure analysis techniques for descriptor generation and clustering of large combinatorial libraries./. Mol. Graph. 2000, 38, 452-463. 

Enumerating the product space of combinatorial libraries and calculating the descriptors can be expensive computationally. Recently, Downs and Barnard [62] have described an efficient method of generating fingerprint descriptors of the molecules in a combinatorial library without the need for enumeration of the products. This method is based on earlier technology for handling Markush structures. An alternative approach is to use random sampling techniques to derive a statistical model of the property under consideration [63],... 

Barnard, J.M., Downs, G.M., Willett, P., Tyrrell, S.M. and Turner, D.B. Rapid diversity analysis in combinatorial libraries using Markush structure techniques. 213th ACS National Meeting, San Francisco, California, April 13, 1997. 

A graphic-oriented interpreter has been designed to control the input of the query structures, the retrieval procedure and the presentation of the answers. This software technology enables the user to customise the menu and to introduce new commands. A hierarchic multiwindow technique facilitates the construction of complex Markush queries. 

Since in the decision tree related structures are located in non-distant parts of the tree, the system is well suited to the simultaneous retrieval of a set of similar structures, therefore the HTSS system is able to retrieve very complex Markush queries with good response times. A biographical multiwindow technique has been implemented in the user interface of the HTSS system to enable the easy entry of Markush queries. Functional groups can be defined by the user as special atom types. 

Arbitrariness and ambiguity of generic forms have prevented the application of many techniques established for specific substance systems. It is not practical to try to describe all t3q>es of generic names in terms of specific names, because the number of them is frequently unreasonably excessive as seen in Markush formulae, e.g., substituted benzene, used in patent documents. 

As we mentioned earlier, the time that is available for each diversity task will likely depend on the nature of the task. Reagent selection may need to be done in a hurry, whereas compound acquisition studies may be afforded rather more time. In the former case, it is clear that the computer time required for diversity analysis/library design must not exceed that available (possibly only days if the library chemistry is already developed, longer if the chemistry is new). For many product-based reagent selection approaches, CPU time is at present a very real obstacle to what might be done. It is to be hoped that more efficient algorithms and exploitation of parallel computation techniques will help alleviate the current difficulties. More fundamentally, the development of approaches based on Markush representations may offer a solution in instances where only simple 2-D descriptors are employed. ... 

J. Barnard and G. Downs. Use of Markush structure techniques to avoid enumeration in diversity analysis of large combinatorial libraries, http //www.daylight.com/meetings/mug97/ Barnard/970227JB.html, 1997. 

Most of the descriptors discussed in this review require an enumerated structure, i,e., the full connection table of the reference molecule. For combinatorial libraries and for certain kinds of descriptors, this is not necessary. Downs and Barnard have recently presented an elegant method to compute molecular fingerprints based on the precursors, using techniques developed for Markush structure handling in chemical patents,... 

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