Patent US4507230A successfully refreshed from Google Patents.
US4507230A
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Peptide synthesis reagents and method of use
Assignee: Research Corp
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Filing: 1982-05-12
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Granted: 1985-03-26
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Expires: 2002-05-12
Abstract
Abstract A method of releasing a functional group present in an amino acid or amino acyl residue from a resin or protecting residue which is bonded to the functional group by a linkage having proton affinity, which comprises: reacting the functional group bonded to the organic residue, with a mixture of HF and a base for a time and under conditions effective to produce the release; wherein the amounts of HF and base in the mixture are adjusted so that said release occurs substantially by an S N 2 mechanism.
Inventors
- 👤 James P. Tam
- 👤 William F. Heath, Jr.
- 👤 Robert B. Merrifield
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 22:07
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/605; C07K1/00; C07K1/04; C07K1/042; C07K1/12
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
110 words
In a method of synthesizing peptides by the solid phase methodology, wherein the growing peptide chain is covalently attached by a functional group through a linkage having proton affinity, to the organic residue of a resin, the improvement wherein said peptide is detached from said resin using a mixture of HF and a base selected from the group consisting of di-C 1 -C 1O -alkyl sulfides and alkyl phenyl sulfides, wherein the amounts of HF and base in said mixture are adjusted so that said detachment occurs predominantly by an S N 2 mechanism, said HF being present in said mixture in an amount between 0.1 and 60% by volume.
Claim 2
Dependent Claim
110 words
In a method of synthesizing peptides by the solid phase methodology, wherein the growing peptide chain is covalently attached by a functional group through a linkage having proton affinity, to the organic residue of a resin, the improvement wherein said peptide is detached from said resin using a mixture of HF and a base selected from the group consisting of di-C 1 -C 1O -alkyl sulfides and alkyl phenyl sulfides, wherein the amounts of HF and base in said mixture are adjusted so that said detachment occurs predominantly by an S N 2 mechanism, said HF being present in said mixture in an amount between 0.1 and 60% by volume.
Claim 3
Dependent Claim
15 words
The method of claim 1 wherein said base also serves as diluent in said mixture.
Claim 4
Dependent Claim
16 words
The method of claim 1 wherein said base has a pKa of between -2 and -11.
Claim 5
Dependent Claim
11 words
The method of claim 1 wherein said dialkylsulfide is dimethyl sulfide.
Claim 6
Dependent Claim
18 words
The method of claim 1 wherein said linkage having proton affinity is an ester, ether or carbamate linkage.
Claim 7
Dependent Claim
25 words
The method of claim 1 wherein said HF is present in said mixture in an amount sufficient to protonate at least 1% of said linkage.
Claim 8
Dependent Claim
27 words
The method of claim 1 wherein said HF is present in said mixture in an amount such that detectable amounts of unprotonated base remain in the solution.
Claim 9
Dependent Claim
14 words
The method of claim 7 wherein said base is protonated no more than 99%.
Claim 10
Dependent Claim
30 words
The method of claim 1 wherein the mixture further comprises about 1 to about 20 percent by volume of scavengers for carbocations including phenols, indoles, ethers, thioethers, thiophenols and sulfides.
Claim 11
Dependent Claim
22 words
The method of claim 1 wherein said mixture also contains 1-50% by volume of a compound capable of swelling a polymeric resin.
Claim 12
Dependent Claim
20 words
The method of claim 1 wherein said functional group is --COOH, --NH 2 , --SH, --OH, >NH, --S-- or ##STR9##
Claim 13
Dependent Claim
13 words
The method of claim 1 wherein said mixture also comprises a polar solvent.
Claim 14
Dependent Claim
16 words
The method of claim 1 wherein the organic residue of said resin is a benzyl residue.
Claim 15
Dependent Claim
12 words
The method of claim 1 wherein said resin is a polystyrene resin.
Claim 16
Dependent Claim
28 words
The method of claim 1 wherein said mixture is a binary mixture comprising HF and dimethylsulfide, wherein the HF is present in said mixture in 0.1-60% by volume.
Claim 17
Dependent Claim
28 words
The method of claim 1 wherein said mixture also contains between 1 and 10% by volume of a C 1 -C 10 alkyl thiol or any aryl thiol.
Claim 18
Dependent Claim
15 words
The method of claim 14 wherein said mixture contains 1-20% by volume of a phenol.
Claim 19
Dependent Claim
34 words
The method of claim 1 which, after said reaction of said mixture with said peptide, comprises the additional step of reacting said peptide with HF at a concentration of greater than 60% by volume.
Claim 20
Dependent Claim
31 words
In the method of claim 1 wherein said peptide is selected from the group consisting of C-terminal-pentapeptide amide of gastrin, cecropin A (1-33), glucagon, Tyr 22 -glucagon, and human gastrin (1-17).
References Cited (Backward Citations)
US4062815A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-03-25 | 1988-09-24 | 1989-03-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-03-25 | 1992-09-24 | 1993-03-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-03-25 | 1996-09-24 | 1997-03-26 | $7700.00 | Window Closed / Lapsed |