Method of designing a peptide and/or peptide derivative for modulating gamma-c-cytokine activity
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Publication Number
US-10227382-B2
Publication Date
2019-03-12
Expiration Date
Abstract
The γc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Peptide and/or peptide derivative antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity are described. Also described are peptide and/or peptide derivative antagonists exhibiting Simul-Block activity, and inhibiting the activity of multiple γc-cytokine family members.
Core Innovation
The invention provides a computer-assisted method of designing a peptide or peptide derivative configured to modulate b3-cytokine activity. The method uses a computer to obtain, from an amino acid sequence database, amino acid sequences of a b3c-box D-helix region of at least two interleukin (IL) proteins, and the peptide or peptide derivative sequence is assembled to comprise partial sequences of the b3c-box D-helix regions from the at least two IL proteins.
The assembled peptide or peptide derivative sequence comprises 11 to 50 amino acids. The design is based on partial sequences of the b3c-box D-helix regions and includes assembling partial sequences into a peptide or peptide derivative configured to modulate one or more b3-cytokines.
A peptide exemplified as BNZ-b3 (SEQ ID NO:1) is described as a composite derived from IL-2/IL-15 b3c-box motifs, with a core motif identified as SEQ ID NO:2. The invention reports that BNZ-b3 suppresses IL-15- and IL-9-driven proliferation and inhibits IL-15-induced STAT5 phosphorylation, and proposes Simul-Block behavior to inhibit multiple b3-cytokines.
Claims Coverage
The document includes one independent claim describing a computer-assisted method for designing a b3c-cytokine-modulating peptide or peptide derivative. The independent claim has multiple dependent refinements that introduce additional constraints on the selected IL sources, assembled sequence structure, patterning, identity thresholds, and b3-cytokine targets.
Computer-assisted obtainment of b3c-box D-helix sequences from IL proteins
Using a computer to obtain from an amino acid sequence database amino acid sequences of a b3c-box D-helix region of at least two interleukin (IL) proteins.
Assembly of a partial-b3c-box D-helix peptide of 11 to 50 amino acids
Assembling the peptide or peptide derivative comprising a sequence comprising partial sequences of the b3c-box D-helix regions of the at least two IL proteins, wherein the peptide or peptide derivative sequence comprises 11 to 50 amino acids.
Synthesis and design to modulate one or more b3-cytokines
Synthesizing by solid-phase peptide synthesis, biological synthesis, or both, the peptide or peptide derivative, thereby designing the peptide or peptide derivative configured to modulate the activity of one or more b3-cytokines.
Overall, the claim coverage centers on using database-derived b3c-box D-helix sequences from at least two interleukin proteins, assembling partial D-helix-derived sequences into an 11 to 50 amino acid peptide or derivative, and synthesizing the designed peptide or derivative for b3-cytokine activity modulation. Dependent claims further narrow IL protein sources, assembled structural and block constraints, sequence patterning, reference identity thresholds, and the specific b3-cytokine targets.
Stated Advantages
BNZ-b3 suppresses IL-15- and IL-9-driven proliferation and inhibits IL-15-induced STAT5 phosphorylation.
The approach proposes Simul-Block behavior to inhibit multiple b3-cytokines.
Documented Applications
No documented applications found
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