Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing
|Title:||Synthesis of cyclic peptides|
|Abstract:||A process for preparing and purifying cyclic peptides having disulfide moieties in a single processing operation which simplifies synthesis and reduces production costs, yet produces high, quality yield. Higher yields are obtained by isolating the desired cyclic compound through direct ion exchange chromatography as an integral part of the single process. The improved process is particularly useful for the preparation of vasopressin and oxytocin and their respective derivatives and analogs.|
|Inventor(s):||Andersson; Lars Henrik Harald (Lund, SE), Skoldback; Jan-Ake (Malmo, SE)|
|Assignee:||Ferring AB (Malmo, SE)|
|Filing Date:||Jun 20, 1996|
|Claims:||1. A method for preparing and purifying cyclic peptide compounds containing a disulfide moiety, comprising: |
a) forming a first solution by adding to a protic solvent at neutral or acidic pH, a non-cyclic peptide containing at least two reactive, protected or non-protected sulfhydryl groups;
b) forming a second solution of iodine dissolved in a protic solvent;
c) introducing said second solution containing iodine to said first solution containing said non-cyclic peptide such that the amount of iodine present in the resulting mixture is at least about stoichiometric with respect to the sulfhydryl groups;
d) allowing the mixture resulting from step (c) sufficient time for disulfide moiety formation and conversion of said non-cyclic peptide to said cyclic peptide compound;
e) adding the mixture from step (d) containing said cyclic peptide compound directly to a separation column containing cation exchange resin;
f) eluting said cyclic peptide compound; and
g) isolating said cyclic peptide compound.
2. The method of claim 1, wherein said non-cyclic peptide in its protonated form has an acidity constant (pK.sub.a) of approximately 7.5 or higher.
3. The method of claim 1, wherein said non-cyclic peptide in its protonated form has an acidity constant (pK.sub.a) of approximately 10 or higher.
4. The method of claim 1, wherein said non-cyclic peptide in its protonated form has an acidity constant (pK.sub.a) of approximately 12 or higher.
5. The method of claim 1, wherein said non-cyclic peptide is:
6. The method of claim 1, wherein said disulfide moiety formation reaction (d) is carried out below approximately 50.degree. C.
7. The method of claim 1, wherein said second solution (b) contains a stoichiometric excess of iodine.
8. The method of claim 1, wherein said cyclic peptide compound is eluted (f) with an aqueous buffer solution selected from the group consisting of ammonium acetate, acetic acid, and combinations of ammonium acetate and acetic acid.
9. The method of claim 1, wherein said isolated cyclic peptide compound is selected from the group consisting of vasopressin and oxytocin.
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.