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United States Department of Agriculture

Agricultural Research Service

Title: Synthesis of (S)-3-(1-Hydroxy-P-Carboran-12-Yl)alanine, a Hydrophobic Tyrosin-Mimetic Amino Acid for Peptides

Authors
item Ujvary, Istvan - HUNGARIAN ACAD OF SCIENCE
item Nachman, Ronald

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 11, 2001
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, wherever it might be located in the chain of a neuropeptide. Tyrosine is found in several insect neuropeptide families that regulate critical life functions in insects. However, this versatile 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, 3-[1-hydroxy-1, 12- dicarba-closo-dodecaboran (12)-12-yl] alanine was prepared from protected 3-[1-hydroxy-1, 12-dicarba-closo-dodecaboran (12)-12-yl] propionic acid in five steps using Oppolzer's sultam methodology for asymmetric hydroxyamination as the key step. The tyrosine mimetic can function as a hydrophobic surrogate for tyrosine residues in insect and mammalian neuropeptides to enhance the lipophilicity, and therefore, the cuticle and/or tissue permeability properties of mimetic analogs. As an amino acid, insertion of the mimic is not limited to the N-terminus, but can replace a tyrosine residue at any position within a peptide sequence.

Last Modified: 11/27/2014
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