US3929758A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Cyclization of cysteine-containing peptides
Assignee: Aventis Pharmaceuticals Inc
•
Filing: 1974-09-12
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Granted: 1975-12-30
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Expires: 1994-09-12
Abstract
Abstract The synthesis of a disulfide cyclic peptide by preparing peptide containing at least two cysteine moieties in its amino acid chain one of which is protected by an n-alkylthio group, and subjecting such peptide to a procedure in which the peptide is held in solution substantially free of oxygen at a pH of from about 5 to 10 until rearrangement takes place to yield a cyclic disulfide peptide and to displace said n-alkylthio group from said amino acid chain. The disclosure also embraces said non-cyclic peptides as new compounds and the processes by which they are perpared.
Inventors
- 👤 John Lawrence Hughes
- 👤 Jay Kenneth Seyler
- 👤 Robert Chung-Huang Liu
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 23:22
CPC Classifications
C; C07; C07K; C07K1/00; C07K1/06; C07K1/061; C07K1/067; C07K14/00; C07K14/435; C07K14/575; C07K14/585; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/15; Y10S930/16; Y10S930/26
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
82 words
IN A PROCESS FOR PREPARING A PEPTIDE HAVING A DISULFIDE RING STRUCTURE, THE STEP OF HOLDING A PEPTIDE WHICH CONTAINS AT LEAST TWO CYSTEINE MOIETIES IN ITS AMINO ACID CHAIN ONE OF WHICH CONTAINS A FREE SULFHYDRYL FUNCTION AND THE OTHER HAVING ITS SULFHYDRYL FUNCTION PROTECTED BY AN N-ALKYLTHIO GROUP WHICH PARTICIPATES IN A DISULFIDE BOND WITH THE THIOL FUNCTION OF SAID OTHER MOIETY IN A SOLUTION SUBSTANTIALLY FREE OF OXYGEN UNTIL REARRANGEMENT HAS TAKEN PLACE TO YIELD THE CYCLIC DISULFIDE PEPTIDE.
Claim 2
Dependent Claim
82 words
IN A PROCESS FOR PREPARING A PEPTIDE HAVING A DISULFIDE RING STRUCTURE, THE STEP OF HOLDING A PEPTIDE WHICH CONTAINS AT LEAST TWO CYSTEINE MOIETIES IN ITS AMINO ACID CHAIN ONE OF WHICH CONTAINS A FREE SULFHYDRYL FUNCTION AND THE OTHER HAVING ITS SULFHYDRYL FUNCTION PROTECTED BY AN N-ALKYLTHIO GROUP WHICH PARTICIPATES IN A DISULFIDE BOND WITH THE THIOL FUNCTION OF SAID OTHER MOIETY IN A SOLUTION SUBSTANTIALLY FREE OF OXYGEN UNTIL REARRANGEMENT HAS TAKEN PLACE TO YIELD THE CYCLIC DISULFIDE PEPTIDE.
Claim 3
Dependent Claim
16 words
A process as set forth in claim 1 in which said solution is an aqueous solution.
Claim 4
Dependent Claim
17 words
A process as set forth in claim 1 in which said solution is an aqueous alcoholic solution.
Claim 5
Dependent Claim
23 words
A process as set forth in claim 1 in which said alkyl group in said n-alkylthio group is ethyl, methyl, propyl or butyl.
Claim 6
Dependent Claim
15 words
A process as set forth in claim 4 in which said alkyl group is ethyl.
Claim 7
Dependent Claim
19 words
A process as set forth in claim 1 which includes the step of agitating said solution during said rearrangement.
Claim 8
Dependent Claim
18 words
A process as set forth in claim 1 including conducting said rearrangement under a stream of inert gas.
Claim 9
Dependent Claim
13 words
A process as set forth in claim 7 wherein said gas is nitrogen.
Claim 10
Dependent Claim
28 words
A process as set forth in claim 7 which includes continuing the process until the gas which has passed over said solution has become substantially free of mercaptan.
Claim 11
Dependent Claim
29 words
A process as set forth in claim 1 in which said peptide is H-CYS-THR-ILE-GLN-ASN-CYS-PRO-LEU-GLY-NH2 in which one of the CYS groups contained therein has bonded thereto the group -S-n-alkyl.
Claim 12
Dependent Claim
13 words
A process as set forth in claim 1 in which said peptide is
Claim 13
Dependent Claim
29 words
A process as set forth in claim 1 in which said peptide is H-ALA-GLY-CYS-LYS-ASN-PHE-PHE-TRP-LYS-THR-PHE-THR-SER-CYS-OH in which one of the CYS groups contained therein has bonded thereto the group -S-n-alkyl.
Claim 14
Dependent Claim
29 words
A process as set forth in claim 1 in which said peptide is H-CYS-TYR-PHE-GLN-ASN-CYS-PRO-ARG-GLY-NH2 in which one of the CYS groups contained therein has bonded thereto the group -S-n-alkyl.
Claim 15
Dependent Claim
13 words
A process as set forth in claim 1 in which said peptide is
Claim 16
Dependent Claim
13 words
A process as set forth in claim 1 in which said peptide is
Claim 17
Dependent Claim
13 words
A process as set forth in claim 1 in which said peptide is
Claim 18
Dependent Claim
13 words
A process as set forth in claim 1 in which said peptide is
Claim 19
Dependent Claim
25 words
A process as set forth in claim 1 in which said peptide is held in said solution at a pH of from 5 to 10.
Claim 20
Dependent Claim
25 words
A process as set forth in claim 17 in which said peptide is held in said solution at a pH of from 6.0 to 8.5.
Claim 21
Dependent Claim
23 words
A process as set forth in claim 18 in which said peptide is held in said solution at a pH of about 7.5.
Claim 22
Dependent Claim
91 words
A process as set forth in claim 1 which includes the steps of coupling one cysteine moiety into an amino acid chain while protecting the sulfhydryl function of said one moiety with a BZ group selected from the class consisting of benzyl, 4-methoxybenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 4-chlorobenzyl, 2,6-dichlorobenzyl, 4-nitrobenzyl and benzylhydryl, and coupling another cysteine moiety into said chain while protecting the sulfhydryl function of said other moiety with an n-alkylthio group, and treating the peptide so formed with anhydrous acid to cleave said BZ group while leaving said n-alkylthio group attached.
Claim 23
Dependent Claim
21 words
A process as set forth in claim 21 in which said chain includes the following sequence of amino acid moieties: CYS-TYR-ILE-GLN-ASN-CYS-PRO-LEU-GLY
Claim 24
Dependent Claim
20 words
A process as set forth in claim 21 in which said chain includes the following sequence of amino acid moieties:
Claim 25
Dependent Claim
21 words
A process as set forth in claim 21 in which said chain includes the following sequence of amino acid moieties: ALA-GLY-CYS-LYS-ASN-PHE-PHE-TRP-LYS-THR-PHE-THR-SER-CYS
Claim 26
Dependent Claim
23 words
A process as set forth in claim 21 in which the alkyl group of said n-alkylthio group is ethyl, methyl, propyl or butyl.
Claim 27
Dependent Claim
15 words
A process as set forth in claim 25 in which said alkyl group is ethyl.
Claim 28
Dependent Claim
33 words
A peptide having an amino acid chain containing two cysteine moieties one of which has a free sulfhydryl function and the other of which has its sulfhydryl function protected by an n-alkylthio group.
Claim 29
Dependent Claim
33 words
A peptide having an amino acid chain containing two cysteine moieties one of which has a free sulfhydryl function and the other of which has its sulfhydryl function protected by an n-alkylthio group.
Claim 30
Dependent Claim
20 words
A peptide as set forth in claim 27 in which said amino acid chain is the same as in oxytocin.
Claim 31
Dependent Claim
20 words
A peptide as set forth in claim 27 in which said amino acid chain is the same as in vasopressin.
Claim 32
Dependent Claim
20 words
A peptide as set forth in claim 27 in which said amino acid is the same as in human calcitonin.
Claim 33
Dependent Claim
21 words
A peptide as set forth in claim 27 in which said amino acid chain is the same as in porcine calcitonin.
Claim 34
Dependent Claim
21 words
A peptide as set forth in claim 27 in which said amino acid chain is the same as in bovine calcitonin.
Claim 35
Dependent Claim
20 words
A peptide as set forth in claim 27 in which said amino acid chain is the same as in somatostatin.
Claim 36
Dependent Claim
50 words
A peptide as set forth in claim 27 and in which a cysteine moiety in the 1st position in its amino acid chain has a free sulfhydryl function and a cysteine moiety in the 6th position in its amino acid chain has its sulfhydryl function protected by an n-alkylthio group.
Claim 37
Dependent Claim
50 words
A peptide as set forth in claim 27 and in which a cysteine moiety in the 6th position in its amino acid chain has a free sulfhydryl function and a cysteine moiety in the 1st position in its amino acid chain has its sulfhydryl function protected by an n-alkylthio group.
Claim 38
Dependent Claim
49 words
A peptide as set forth in claim 27 in which a cysteine moiety in the 1st position of its amino acid chain has a free sulfhydryl function and a cysteine moiety in the 7th position in its amino acid chain has its sulfhydryl function protected by an n-alkylthio group.
Claim 39
Dependent Claim
48 words
A peptide as set forth in claim 27 in which a cysteine moiety in the 7th position of its amino acid chain has a free sulfhydryl function and a cysteine moiety in the 1st position in its amino acid has its sulfhydryl function protected by an n-alkyltHio group.
Claim 40
Dependent Claim
48 words
A peptide having an amino acid chain containing two cysteine moieties one of which has it sulfhydryl function protected by an n-alkylthio group and the other having its sulfhydryl function protected by a group selected from the class consisting of benzyl, 4-methoxybenzyl, 3,4-dimethylbenzyl, 4-chlorobenzyl, 2,6-dichlorobenzyl, 4-nitrobenzyl and benzylhydryl.
Claim 41
Dependent Claim
48 words
A peptide having an amino acid chain containing two cysteine moieties one of which has it sulfhydryl function protected by an n-alkylthio group and the other having its sulfhydryl function protected by a group selected from the class consisting of benzyl, 4-methoxybenzyl, 3,4-dimethylbenzyl, 4-chlorobenzyl, 2,6-dichlorobenzyl, 4-nitrobenzyl and benzylhydryl.
References Cited (Backward Citations)
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-12-29 | 1979-06-30 | 1979-12-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-12-29 | 1983-06-30 | 1983-12-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-12-29 | 1987-06-30 | 1987-12-30 | $7700.00 | Window Closed / Lapsed |