Processes for coupling amino acids using bis-(trichloromethyl) carbonate
AssigneePeptor Limited
InventorsEliezer Palb, Tamar Yechezkel, Yoseph Salitra
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Abstract
A process is disclosed for using triphosgene as an efficient and effective coupling reagent during peptide synthesis, by in situ generation of amino acid chloride from a protected amino acid. This process is particularly useful for the coupling to sterically hindered amino acid residues, or for other difficult couplings. Furthermore, the same reagent can be used for the derivatization of peptides by formation of an amide bond between a free amine on a peptide and a carboxylic acid, or for the coupling of an amino acid to a solid support.
Claims2
In the coupling of a carbohydrate moiety to a peptide chain, the improvement which comprises forming an amide bond between a peptide in the peptide chain and the carbohydrate moiety using bis-(trichloromethyl) carbonate, diphosgene or phosgene.
A peptide selected from the group consisting of:
- 17A) PheC2-NMeAla-Ala-AlaN3-NH2;
- 17B) GlyC1-Ala-Lys-(D)Ala-Ala-AlaN3-NH2;
- 18) Ala-Ala-Lys-(D)Ala-Ala-AlaC2-NH2;
- 19A) (D)Ala-AlaN2-Ala-Lys-(D)Ala-Ala-AlaC3-NH2;
- 19B) AlaN2-Ala-Lys-(D)Ala-Ala-AlaC3-NH2;
- 20A) GlyC1-Ala-Lys-(D)Ala-Ala-AlaN2-NH2;
- 20B) PheC2-N-MeAla-Ala-AlaN2-NH2;
- 22) (D)Ala-AlaN2-Ala-Lys-(D)Ala-Ala-AlaC3-NH2;
- 31) TrpC3-Ser-Glu-Tyr-Leu-PheN2-Gln-NH2 (SEQ ID NO:1);
- 37) PheC1-Phe-Phe-(D)Trp-(L)Lys-PheN2-NH2;
- 38) PheC1-Phe-Phe-(D)Trp-(D)Lys-PheN2-NH2;
- 39) PheC1-Phe-Leu-(D)Trp-(D)Lys-PheN2-NH2;
- 41) Biotin-Trp-Arg-Lys-(D)Arg-Phe-AlaC3-NH2;
- 42) PheC1-Ala-Phe-AlaN2-NH2;
- 47) Phe-NMePhe-NMePhe-NH2;
- 48) NMePhe-NMePhe-NMePhe-NH2;
- 51) Thr-AlaC2-Ser-Glu-Asn-His-Leu-Arg-His-Ala-LeuN3-Ser-NH2 (SEQ ID NO:2);
- 52) Thr-AlaC3-Ser-Glu-Asn-His-Leu-Arg-His-Ala-LeuN3-Ser-NH2 (SEQ ID NO:3);
- 56) TrpC3-Ser-Glu-Tyr-LeuN3-Amb-Ala-Arg-NH2 (SEQ ID NO:4);
- and
- 57) Biotin-Trp-Arg-Lys-(D)Arg-Phe-AlaC3-Leu-Arg-(D)Tyr-AlaN3-NH2.
Dependencies are inferred from the claim text.