Synthetic approach to designed chemical structures
AssigneeRegents of the University of Minnesota
InventorsBeulah H. Gray, Judith R. Haseman, Kevin Mayo, Arjan W. Griffioen
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Abstract
This invention relates to the chemical design and production of peptides, peptide structure and three dimensional conformation was assessed using NMR, circular dichroisin and pulsed field gradient NMR. In addition, this invention relates to peptides produced by these methods and to methods for using the peptides.
Claims32
A method for synthesizing a water-soluble peptide having at least about 35% amino acids having hydrophobic side chains, the method comprising combining amino acids having charged side chains and amino acids having noncharged polar side chains with amino acids having hydrophobic side chains, wherein the amino acids having charged side chains are provided in a ratio of at least about 2:1 amino acids having positively charged side chains to amino acids having negatively charged side chains.
A method for synthesizing a water-soluble peptide having at least about 35% amino acids having hydrophobic side chains, the method comprising combining amino acids having charged side chains and less than about 20% amino acids having noncharged polar side chains with amino acids having hydrophobic side chains, wherein:
- (a) the amino acids having charged side chains are provided in a ratio of at least about 2:1 amino acids having positively charged side chains to amino acids having negatively charged side chains;
- (b) the water-soluble peptide has about 35% to about 55% amino acids having hydrophobic side chains;
- and
- (c) at least two of the amino acids having hydrophobic side chains are positioned in the peptide with an intervening turn sequence in a manner such that the two amino acids having hydrophobic side chains are capable of aligning in a pairwise fashion to form a B-sheet structure;
- and
- (d) the turn sequence is LXXGR, wherein each X is independently selected from the group consisting of K, N, S, and D.
A water soluble peptide selected from the group consisting of βpep 1 through βpep-30 (SEQ ID NOS:1-30).
A method for treating a bacteria infection or endotoxic shock comprising administering an amount of a pharmaceutical composition effective to inhibit the bacterial infection or neutralize endotoxin to a mammal, wherein the pharmaceutical composition comprises:
- (a) a peptide demonstrating bactericidal activity or endotoxin neutralizing activity selected from the group consisting of βpep-1 through βpep-30 (SEQ ID NO:
- 1 through SEQ ID NO:30);
- and
- (b) a pharmaceutically acceptible carrier.
A method for inhibiting TNF-α levels in a mammal comprising the step of administering a therapeutically effective amount of a pharmaceutical composition comprising:
- (a) a peptide demonstrating bactericidal activity or endotoxin neutralizing activity selected from the group consisting of βpep-1 through βpep-30 (SEQ ID NO:
- 1 through SEQ ID NO:30);
- and
- (b) a pharmaceutically acceptible carrier.
A method for inhibiting endothelial cell proliferation comprising the step of administering an effective amount of a composition comprising:
- a peptide demonstrating endothelial cell proliferation inhibition selected from the group consisting of βpep-1 through βpep-30 (SEQ ID NO:
- 1 through SEQ ID NO:30).
A method for promoting inter-cellular adhesion molecule expression comprising the step of administering an effective amount of a composition comprising:
- a peptide promoting inter-cellular adhesion molecule expression selected from the group consisting of βpep-1 through βpep-30 (SEQ ID NO:1 through SEQ ID NO:30).
Dependencies are inferred from the claim text.