Peptides causing formation of compact structure

Abstract

The present invention relates to compositions and methods comprising peptides with high mutual affinity that, when attached to a protein, assist the protein to fold into a compact structure. By virtue of its stability and binding, this scaffold extends the activity of any contained protein sequence in the presence of cellular and other proteases. This compact structure may have other included functional sequences, which are superior to linear and less constrained peptides for library screening, building structure-biased peptide libraries, and targeting specific intracellular and extracellular compartments. The compositions of the present invention can be displayed on viral, archaeal, prokaryotic and eukaryotic cell surfaces for library screening, drug screening and display. The methods of the present invention are useful for in vivo screening of intracellular effector proteins that modulate signaling pathways, and for identification of interacting proteins in vitro. Therefore, the present invention can be used as a scaffold for gene therapy, for the isolation of new therapeutic drugs, and has potential utilization value for use as a therapeutic agent in physiological fluids.

Description

field of invention

[0001] The compositions and methods of the invention involve the use of dimerization peptides that can self-associate and their use with other proteins to induce compact structure formation. Background of the invention

[0002] Proteins mostly interact through conformationally restricted domains. Although, as is known in the art, linear peptides with freely rotating amino and carboxy termini can be powerful, converting such peptide structures into pharmacological agents is often difficult. Displaying peptides in conformationally constrained structures can thus yield drugs with high affinity for their target proteins. Constrained peptides have a number of useful features compared to their linear analogs. They include: (i) increased stability to proteolytic hydrolysis due to the absence of unconstrained N- or C-terminal amino acids susceptible to aminopeptidases or carboxypeptidases and a non-extended structure that reduces susceptibility to endopeptidases...

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