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COMPUTATIONAL NEUROPEPTIDE DESIGN AND RECEPTOR MATCHING

$374,982R44FY2000MHNIH

Cielo Institute, Inc., Asheville NC

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Verbatim from the Applicant's Abstract) Proprietary computational and graphical techniques combine elements of eigenvalue and wavelet decompositions, maximum entropy power spectra and "ergodic" measure theoretical methods (useful for the analyses of irregular series in hydrodynamic turbulence and plasma physics) with thermodynamic transformation of the amino acids in broad classes of globular and membrane proteins, including G-protein and tyrosine kinase coupled receptors, transporters, pores and channels. In the proposed work, these methods will be used to: 1) Create a referential, graphical atlas of protein sequence transformations through which to characterize and categorize new nucleotide and protein sequences with weak or absent specific amino acid, database homology. The atlas will be used in commercial consultation with investigators confronted with this problem; 2) From only a receptor's primary sequence, generate completely new libraries of membrane protein-targeted, regulatory peptides; and 3) Survey these algorithmically designed new peptides for sequence dependent potentiating or inhibiting influences on natural ligand-induced physiological activity, as demonstrated by microphysiometric assays of native or receptor cDNA transfected cell systems. The resulting physiologically active, patentable peptides will be used in commercial collaboration with research laboratories searching for probes of membrane protein allosteric sites and with drug companies developing respiratory delivery systems for peptide drugs. PROPOSED COMMERCIAL APPLICATION: We are using novel algorithmic techniques to design novel peptides that modulate the function of receptors and other proteins. There are two commercial applications of our work: (1) The licensing of our patented (in process) methods of peptide drug design to pharmaceutical firms; (2) The licensing of our new protein-targeted peptides for use in basic research and clinical testing and potential clinical use by pharmaceutical firms.

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