Self-Assembling Peptides Incorporating Modifications and Methods of Use Thereof

Abstract

The invention provides a self-assembling peptide comprising (a) a first amino acid domain that mediates self-assembly, wherein the domain comprises alternating hydrophobic and hydrophilic amino acids that are complementary and structurally compatible and self-assemble into a macroscopic structure when present in unmodified form; and (b) a second amino acid domain that does not self-assemble in isolated form. In certain embodiments of the invention the second amino acid domain comprises a biologically active peptide motif, e.g., a peptide motif found in a naturally occurring protein, or a target site for an interaction with a biomolecule. In certain embodiments of the invention the naturally occurring protein is a component of the extracellular matrix, e.g., a component of the basement membrane. The invention further provides scaffolds comprising the self-assembling peptides and methods of using the scaffolds including for cell culture, tissue engineering, and tissue repair.

1 - 69 . (canceled) 
     
     
         70 . A self-assembling peptide comprising:
 (a) a first amino acid domain that mediates self-assembly, wherein the domain comprises alternating hydrophobic and hydrophilic amino acids that are complementary and structurally compatible, and that self-assemble into a macroscopic structure when present in unmodified form, which sequence is SEQ ID NO: 4 (RAD16-I); and   (b) a second amino acid domain, wherein the sequence of the second amino acid domain comprises SEQ ID NO: 35 (RYVVLPR); and
 wherein the peptide forms a beta sheet upon self-assembly. 
   
     
     
         71 . The self-assembling peptide of  claim 70 , wherein the first and second amino acid domains are joined by a peptide bond. 
     
     
         72 . The self-assembling peptide of  claim 70 , wherein the first and second amino acid domains are covalently or non-covalently cross-linked to one another. 
     
     
         73 . The self-assembling peptide of  claim 72 , wherein the linker domain comprises one or more glycine residues.