Back to results
US 2010/0137559 A1Published application
Process for production of cyclic peptides
OwnerAvi TOVI, Chaim Eidelman +3inventors
InventorsAvi TOVI, Chaim Eidelman, Shimon Shushan, Shai Elster, Hagi Alon
Life of this patent
Estimating the term…
Abstract
The invention relates to methods for the preparation of polypeptides. The polypeptides are prepared in high purity of at least about 98.5%, and preferably at least about 99% by HPLC.
Claims34
A process for preparing cyclic peptides comprising the steps of:
- a) providing a protected linear peptide containing at least two protected thiol-containing residues of which at least one thiol-containing residue is protected with an orthogonal protecting group;
- b) reacting the protected linear peptide with an acidic composition to produce a semi-protected linear peptide with the orthogonal protecting group on one of the thiol-containing residues;
- c) purifying the semi-protected linear peptide;
- d) treating the purified semi-protected linear peptide obtained in step (c) with an oxidizing agent to produce a cyclic peptide;
- and
- e) purifying the cyclic peptide to obtain a purified cyclic peptide.
3 more elements
A process for synthesizing octreotide comprising the steps of:
- a) providing a protected linear peptide having the formula X-D-Phe-Cys(X)-Phe-D-Trp-Lys(X)-Thr(X)-Cys(Acm)-Thr(X)-ol, wherein X is a same or different protecting group;
- b) reacting the protected linear peptide of step (a) with an acidic composition to produce a semi-protected linear peptide D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys(Acm)-Thr-ol;
- c) purifying the semi-protected linear peptide of step (b) using HPLC;
- d) treating the purified semi-protected linear peptide of step (c) with an oxidizing agent to produce a cyclic peptide (2,7 cyclic) D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;
- and
- e) purifying the cyclic peptide of step (d) using HPLC to obtain a purified cyclic peptide.
3 more elements
A process for synthesizing eptifibatide comprising the steps of:
- a) providing a protected linear peptide having the formula Mpa(X)-Har(X)-Gly-Asp(X)-Trp-Pro-Cys(Acm), wherein X is a same or different protecting group;
- b) reacting the protected linear peptide of step (a) with an acidic composition to produce a semi-protected linear peptide Mpa-Har-Gly-Asp-Trp-Pro-Cys(Acm)-NH2;
- c) purifying the semi-protected linear peptide of step (b) using HPLC;
- d) treating the purified semi-protected linear peptide of step (c) with an oxidizing agent to produce a cyclic peptide (1,7 cyclic) Mpa-Har-Gly-Asp-Trp-Pro-Cys(Acm)-NH2;
- and
- e) purifying the cyclic peptide of step (d) using HPLC to obtain a purified cyclic peptide.
3 more elements
A process for synthesizing desmopressin comprising the steps of:
- a) providing a protected linear peptide having the formula Mpa(X)-Tyr(X)-Phe-Gln(X)-Asn(X)-Cys(Acm)-Pro-D-Arg(X)-Gly, wherein X is a same or different protecting group;
- b) reacting the protected linear peptide of step (a) with an acidic composition to produce a semi-protected linear peptide Mpa-Tyr-Phe-Gln-Asn-Cys(Acm)-Pro-D-Arg-Gly-NH2;
- c) purifying the semi-protected linear peptide of step (b) using HPLC;
- d) treating the purified semi-protected linear peptide of step (c) with an oxidizing agent to produce a cyclic peptide (1,6 cyclic) Mpa-Tyr-Phe-Gln-Asn-Cys(Acm)-Pro-D-Arg-Gly-NH2;
- and
- e) purifying the cyclic peptide of step (d) using HPLC to obtain a purified cyclic peptide.
3 more elements
A process for synthesizing calcitonin salmon comprising the steps of:
- a) providing a protected linear peptide having the formula Cys(X)-Ser(X)-Asn(X)-Leu-Ser(X)-Thr(X)-Cys(Acm)-Val-Leu-Gly-Lys(X)-Leu-Ser(X)-Gln(X)-Glu(X)-Leu-His(X)-Lys(X)-Leu-Gln(X)-Thr(X)-Tyr(X)-Pro-Arg(X)-Thr(X)-Asn(X)-Thr(X)-Gly-Ser(X)-Gly-Thr(X)-Pro, wherein X is a same or different protecting group;
- b) reacting the protected linear peptide of step (a) with an acidic composition to produce a semi-protected linear peptide Cys-Ser-Asn-Leu-Ser-Thr-Cys(Acm)-Val-Leu-Gly-Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-Gly-Thr-Pro-NH2;
- c) purifying the semi-protected linear peptide of step (b) using HPLC;
- d) treating the purified semi-protected linear peptide of step (c) with an oxidizing agent to produce a cyclic peptide (1,7 cyclic) Cys-Ser-Asn-Leu-Ser-Thr-Cys(Acm)-Val-Leu-Gly-Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-Gly-Thr-Pro-NH2;
- and
- e) purifying the cyclic peptide of step (d) using HPLC to obtain a purified cyclic peptide.
3 more elements
Octreotide having a purity of at least about 98.5% by HPLC.
Eptifibatide having a purity of at least about 98.5% by HPLC.
Desmopressin a purity of at least about 98.5% by HPLC.
Calcitonin salmon having a purity of at least about 98.5% by HPLC.
Dependencies are inferred from the claim text.