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United States Department of Agriculture

Agricultural Research Service

Title: Synthesis of 3-(12-Hydroxy=p-Carboranyl) Propionic Acid, a Hydrophobic, N-Terminal Tyryosine-Mimetic for Peptides

Authors
item Ujvary, Istvan - HUNGARIAN ACAD OF SCIENCE
item NACHMAN, RONALD

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 22, 2000
Publication Date: N/A

Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling such pests. The basic premise of this research is that peptides (short chains of amino acids) serve as potent internal messengers in insects to regulate vital functions. Peptides themselves are unsuitable for control measures due to their instability to enzymes in the circulatory and digestive systems, and an inability to penetrate the outer surface of the insect. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that actively inhibit or over-stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. In this paper, we describe the design and synthesis of a new mimic (or surrogate) for the amino acid tyrosine, when it is located at the end of a peptide chain. Tyrosine is found in several insect neuropeptide families that regulate critical life functions in insects. However, this mimic, made from the ball-shaped carborane molecule, is a highly oily material. When incorporated into an insect neuropeptide, it can confer soap-like qualities that enhance its ability to penetrate the outer surface of the insect. This work leads us one step closer to the development of practical neuropeptide-like agents that will be effective in controlling certain pests in an environmentally friendly fashion.

Technical Abstract: A new, p-carborane containing analog of tyrosine, namely 3-[1- hydroxy-1, 12-dicarba-closo-dodecaboran (12)-12-yl] propionic acid was prepared from p-carborane in five steps involving hydroxypropylation of O-protected 1-hydroxy-p-carborane as the key transformation. The simple tyrosine mimetic can function as a hydrophobic surrogate for an N-terminal tyrosine residue in insect and mammalian neuropeptides to enhance the lipophilicity, and therefore, the cuticle and/or tissue permeability properties of mimetic analogs.

Last Modified: 8/19/2014
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