MHC-I Restricted Epitopes Containing Non-Natural Amino Acid Residues
AssigneePurdue Pharma L.P.
InventorsDonald J. KYLE, Daniel A. Soltis, Lynda G. Tussey
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Abstract
The invention provides for the synthesis of more effective generators of a T-cell immune response by providing peptide derivatives that are MHC class I-restricted antigens. The peptide derivatives of the present invention are prepared or derived from a parent peptide of 8 to 11 amino acid residues in length, wherein the peptide derivative contains a non-natural amino acid substituted in place of a naturally-occurring amino acid residue at one or more primary anchor positions in the parent peptide or at position 6, position 7, or the C-terminus.
Claims11
1-27. (canceled)
A complex comprising an MHCI having a peptide derivative bound within its antigen-binding groove, wherein the peptide derivative is selected from the group consisting of:
- (a) a peptide derivative having the general formula A-Xaa-GIGILTV (SEQ ID NO:3), wherein Xaa is a non-natural amino acid that provides increased conformational constraint in the peptide derivative compared to the conformational constraint present in the parent peptide having amino acid sequence AAGIGILTV (SEQ ID NO:1), wherein Xaa is selected from the group consisting of [c3a], [c5g], [chg], [cpg], [dfb], [dhl], [phg], and [sta];
- (b) a peptide derivative having the general formula E-Xaa-AGIGILTV (SEQ ID NO:12), wherein Xaa is a non-natural amino acid that provides increased conformational constraint in the peptide derivative compared to the conformational constraint present in the parent peptide having amino acid sequence EAAGIGILTV (SEQ ID NO:2), wherein Xaa is selected from the group consisting of [c3a], [c5g], [chg], [cpg], [dfb], [dhl], [phg], and [sta];
- (c) a peptide derivative having the general formula I-Xaa-TFKNWPF (SEQ ID NO:22), wherein Xaa is a non-natural amino acid that provides increased conformational constraint in the peptide derivative compared to the conformational constraint present in the parent peptide having amino acid sequence ISTFKNWPF (SEQ ID NO:21), wherein Xaa is selected from the group consisting of [c3a], [c5g], [chg], [cpg], [dfb], [dhl], [phg], and [sta];
- and
- (d) a peptide derivative having the general formula K-Xaa-RRAIEQL (SEQ ID NO:32), wherein Xaa is a non-natural amino acid that provides increased conformational constraint in the peptide derivative compared to the conformational constraint present in the parent peptide having amino acid sequence KVRRAIEQL (SEQ ID NO:31), wherein Xaa is selected from the group consisting of [c3a], [c5g], [chg], [cpg], [dfb], [dhl], [phg], and [sta].
29-73. (canceled)
Dependencies are inferred from the claim text.