PEPTIDE-RESIN CONJUGATE AND USE THEREOF

摘要

The present invention relates to a peptide-resin conjugate of Formula (2), wherein: Pr1 is selected from H, alkyl, aryl, aralkyl, acyl, aroyl and a protecting group; Y is a direct bond; or an optionally protected natural or unnatural amino acid residue; or a peptide comprising 2 to 200 natural or unnatural amino acid residues, each of which is optionally protected; Dia is a natural or unnatural diamino acid; A is a polymer resin conjugated to the side chain amino function of the diamino acid; X is an optionally protected natural or unnatural amino acid residue; or a peptide comprising 2 to 15 natural or unnatural amino acid residues, each of which is optionally protected; R1, and R2 are each independently selected from H, alkyl, aryl, aralkyl, NH2, NH—CO—NH2. Further aspects of the invention relate to a process of preparing peptide-resin conjugates of Formula (2), and their use in the preparation of peptides.;

主权项

1. A peptide-resin conjugate of Formula (2′), wherein: Pr1 is selected from H, alkyl, aryl, aralkyl, acyl, aroyl and a protecting group; Y is a natural or synthetic peptide comprising two or more natural or unnatural amino acid residues, wherein each of said natural or unnatural amino acid residues is optionally protected, and wherein said natural or synthetic peptide is selected the following: [1] 3-Mercaptopropionyl-D-Tyr(Et)-Ile-Thr-Asn-Cys-Pro-; [2] Arg-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-; [3] Cys-Tyr-Phe-Gln-Asn-Cys-Pro-; [4] Gly-Gly-Gly-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-; [5] 3-Mercaptopropionyl-Tyr-Phe-Gln-Asn-Cys-Pro-; [6] Pyr-His-Trp-Ser-Tyr-D-Trp-Leu-; [7] Pyr-His-Trp-Ser-Tyr-D-2-Nal-Leu-; [8] Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-; [9] Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-; [10] Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-; [11] Pyr-His-Trp-Ser-Tyr-D-His(Bzl)-Leu-; [12] Pyr-His-Trp-Ser-Tyr-D-Trp-Leu-; [13] D-2-Nal-4-chloro-D-Phe-β-(3-pyridyl)-D-Ala-Ser-Tyr-D-Cit-Leu-; [14] D-2-Nal-D-4-Cpa-D-3-Pal-Ser-N-Me-Tyr-D-Hci-Nle-; [15] Cys-Lys-Gly-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-; [16] Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-; [17] Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-; [18] Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-; [19] Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-; [20] Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Ala-Glu-Asp-Met-Ala-Arg-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-; and [21] Tyr-Pro-Ile-Lys-Pro-Glu-Ala-Pro-Gly-Glu-Asp-Ala-Ser-Pro-Glu-Glu-Leu-Asn-Arg-Tyr-Tyr-Ala-Ser-Leu-Arg-His-Tyr-Leu-Asn-Leu-Val-Thr-Arg-Gln-; Dia is a natural or unnatural diamino acid; A is a polymer resin conjugated to the side chain amino function of the diamino acid; X is an optionally protected natural or unnatural amino acid residue; or a natural or synthetic peptide comprising 2 to 15 natural or unnatural amino acid residues, each of which is optionally protected; R1 and R2 are each independently selected from H, alkyl, aryl, aralkyl, NH2 and NH—CO—NH2.