Biorational

Examination of the various classified listings of herbicides provides iasight iato the processes and approaches that lead to the discovery of new pesticides. The four principal development approaches are random screening, imitative chemistry, testing natural products, and biorational development. 

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

E. R. Hah and. W. Barry, eds., Biorational Pest Control Agents Formulation and Delivery, ACS Symposium Series No. 595, American Chemical Society, Washington, D.C., 1995, 320 pp. 

These investigations illustrate the biorational approach to desirable chemicals, but none of them demanded awareness of such complex interactions as those linking oak trees and Lyme disease. In the future, complicated situations of this sort should be better understood and make their own contribution to biotechnology. This possibility and where it may lead are admirably portrayed by a remarkable discovery involving an ant, a bacterium, and two sorts of fungi. These creatures are the principals in a second tale of ants and antibiotics. 

Methods by which to find a biologically active compound may be classified as (a) random selection/screening (b) directed synthesis (c) natural product models and (d) biorational design. Allelochemical research can be considered as a natural product model. Generally, natural pesticides such as allelochemicals can be the biological compound(s) itself or products or parts of plant tissues. 

The rapidly expanding growth of knowledge of natural product structures now provide clearer understanding of biochemical mechanisms. This has made possible "biorational" approaches to the design of pest control agents. Natural products may be of potential value in pest control in several ways. 

Schuster, D.J. and Stansly, P.A., Response of two lacewing species to biorational and broad-spectrum insecticides, Phytoparasitica, 28, 297, 2000. 

The discovery of these pheromone biosynthesis activating neuropeptides could form the basis for development of new biorational control agents for the disruption of the essential processes of development and reproduction in moths (19). 

Mendelsohn, M.L., T.C. Ellwanger, R.I. Rose, J.L. Kough and P.O. Hutton (1995). Registration of biologicals, in Biorational Pest Control Agents, Formulation and Delivery, F.R. Hall and J.W. Barry (Eds), American Chemical Society, Washington, DC, pp. 20-26. 

In this volume of Annual Plant Reviews, we have tried to provide an up-to-date survey of the biochemistry and physiology of plant secondary metabolism. A companion volume - M. Wink (ed.) Functions of Plant Secondary Metabolites and Biotechnology - published simultaneously provides overviews of the modes of action of bioactive SMs and their use in pharmacology as molecular probes, in medicine as therapeutic agents and in agriculture as biorational pesticides. 

The biorational design of analogous compounds must take into account the asymmetry of 2-hydroxy dodecanoic acid since C-2 is an asymmetric carbon with possible R and S enantiomers. That the stereochemistry appears to be... 

The hydroxylated fatty acids hold the promise of being safe, simple and specific plant protectants. Our work on laetisaric acid demonstrates how the investigation of allelochemical interactions may lead to the development of new biorational agrochemicals. 

As one such activity, EPA s Office of Pesticide Programs (OPP) created the category of Biorational Pesticides (73) to promote the development and use of such agents by simplifying the data requirements for such agents. The agency s stated reason for doing so are as follows ... 

In this proposed classification, some of the relevant factors that distinguish biorational pesticides from conventional pesticides include ... 

Biochemical Pesticides. The characteristics noted above were not specified as being all of the attributes that a biorational pesticide might exhibit, nor was a biorational pesticide required to exhibit all of the cited characteristics. Proposed SS 158.165(a) (3) noted that EPA would make case-by-case decisions on what was or was not a biochemical-type biorational pesticide. This provision was included so that chemicals which are substantially similar to biochemicals but might not technically meet the two criteria established for defining biochemical pest control agents might be none-the-less classified as biochemical pesticides. 

Part 158 in Title 40 of the Code of Federal Regulations was finalized in 1984 (14). In the final rule, the term Biorational Pesticide was dropped and the term Biochemical and Microbial Pesticides was adopted to describe this class of pest control agents (Figure 4). The general characteristics of biochemical and microbial pesticides remained essentially unchanged. 

Figure 4. Relationship between conventional pesticides, biological control agents, and biorational pesticides. (Reproduced from reference 1. Courtesy of Marcel Dekker, Inc.)...

Application of molecular modeling techniques to the biorational design of selective and environmentally safe crop protection chemicals is addressed. Sulfonylurea herbicides are used as an example to illustrate the kinds of biological information that can be known with modern technologies. An example of selective inhibitor design using computer graphics is presented. 

In this chapter, I will address how molecular modeling tools can be applied to the biorational design of selective and... 

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