US 2003/0125518 A1Published application

Surface simulation synthetic peptides useful in the treatment of hyper-variable viral pathogens

OwnerHarry F. Crevecoeurinventor

Life of this patent

Estimating the term…

Loading patent…

Abstract

Synthetic peptides and methods for configuring the amino acid sequences thereof are disclosed which are especially useful in the preparation of vaccines intended for the prophylaxis and treatment of viral pathogens exhibiting high mutation rates such as HIV-1. The high mutation rates of such viral pathogens result in extreme variance in the linear sequence of viral protein residues, such as the variable linear sequences of gp120 of HIV-1. To be effective and provide broad-spectrum and/or cross-clad coverage against hypervariable viruses such as HIV-1, vaccines must target common denominators of all infective strains of such a virus. These functional common denominators lie in the 3-dimensional configuration of proteins essential for host cell binding and infectivity. The disclosed peptides and methods for configuring same are derived from the 3 dimensional relationships of conserved residues of viral proteins defining conformational epitopes necessary and required for viral pathogenicity.

A method for configuring surface simulation synthetic peptides effective in the diagnosis and treatment of hyper-variable viral pathogens comprising:

selecting a protein of said subject pathogenic virus necessary and required for viral pathogenicity having an amino acid sequence;
identifying, within the amino acid sequence of said protein, non-sequential conserved residues required for viral pathogenicity;
subjecting said protein to an imaging scan so as to obtain and record 3 dimensional and spatial relationship data in regards to each of said conserved residues;
subjecting said 3 dimensional image data obtained by said imaging scan to computer analysis via protein analysis software in order to obtain a functional map thereof;
determining, by means of said analytic software program, a 3 dimensional position for each of said non-sequential conserved residues within said viral protein and spatial relationships thereamong;
designing sequences for surface simulation synthetic peptides having amino acid sequences ordered to correspond and approximate the identified 3 dimensional relationships of selected conserved, non-sequential residues in regards to relative 3 dimensional proximity;
utilizing a computer search engine in order to compare said designed surface simulation synthetic peptides with human gene, protein and peptide databases in order to identify and eliminate any such synthetic peptide having an amino acid sequence homologous to peptides in such databases;
further analyzing and evaluating said surface simulation synthetic peptides for antigenicity, hydropathy, accessibility and flexibility thereof utilizing protein analysis software;
modifying the sequence of said surface simulation synthetic peptide in accordance with the results of said software analysis in order to enhance and optimize the antigenicity and accessibility thereof;
preparing surface simulation synthetic peptides whose amino acid sequences are ordered to correspond to the identified 3 dimensional spatial relationships of said conserved residues necessary and required for viral pathogenicity and whose amino acid sequences are further refined to provide optimized antigenicity and accessibility.

7 more elements

Abstract

Claims60