Synthesis of soluble .beta.-sheet forming peptides

DETAILED DESCRIPTION OF THE INVENTION An intricate interplay exists between peptide .
beta.
-sheet formation, self-association, and water solubility.
A challenge in making a soluble folded peptide is that solubility has a double-edged effect: precipitation versus over-solvation.
Precipitation is the falling out of solution of a peptide, while over-solvation is the tendency of a soluble peptide to prefer intermolecular water-peptide interactions over intramolecular folding interactions.
Going too far in either direction (precipitation or over-solvation) destabilizes the folded state.
Reduced solubility generally occurs due to intermolecular peptide-to-peptide interactions (hydrophobic and electrostatic) which results in precipitation or gelation.
Although the precipitate, for example, is in equilibrium with soluble peptide, the equilibrium is shifted away from solution.
If a designed .
beta.
-sheet-forming peptide contains a relatively large number of amino acids with hydrophobic side chains which are not screened to some extent by the folding process, precipitation or gelation may result.
Inherent in the design of .
beta.
-sheet forming peptides, therefore, is the capacity to self-associate, thereby screening hydrophobic surface from solvent water.
The present invention provides a method for the de novo design of peptides that are water soluble at or near physiological conditions and preferably form .
beta.
-sheet structures.
Preferably and advantageously, the water-soluble peptide forms, through self-association, a .
beta.
-sheet in the absence of any intermolecular covalent interactions (although this is not necessarily a requirement).
The method takes into account the following parameters: the number or percentage composition of amino acids with positively and negatively charged side chains, the number or percentage composition of amino acids with noncharged polar side chains, the number or percentage composition of amino acids with hydrophobic side chains, proper placement and pairing of amino acids in the sequence and in space, and specific turn character