US4786684A
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Benzylthioether-linked solid support-bound thiol compounds and method for peptide synthesis
Assignee: Icahn School of Medicine at Mount Sinai
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Filing: 1986-08-21
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Granted: 1988-11-22
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Expires: 2006-08-21
Abstract
Abstract A method for the synthesis of sulfydryl-containing peptides which comprises forming a benzylthioether-linked solid support-bound thiol compound having at least one functional group for generating at least one peptide bond, sequentially coupling at least one protected amino acid or peptide to the compound until a peptide having desired amino acid sequence is obtained, and cleaving the benzylthioether linkage to release the peptide from the support with concomitant regenertion of the sulfydryl group in the peptides. The invention also encompasses compounds having the general formula ##STR1## wherein X is H, NH 2 , ##STR2## or acyl-NHY, said acyl being an amino acid or a peptide; Y is H, COOH, CONHNH 2 , ##STR3## the ester COOR 1 in which R 1 is selected from the group consisting of methyl, ethyl, phenyl, ortho-nitrophenyl and para-nitrophenyl, the amide CONH 2 , or the amide CONHR 2 in which R 2 is an amino acid or peptide; and providing that X and Y cannot both be H.
Inventors
- 👤 John D. Glass
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 14:33
CPC Classifications
C; C07; C07K; C07K1/00; C07K1/06; C07K1/061; C07K1/067; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/26
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
69 words
In a method of synthesizing sulfhydryl-containing peptides, the improvement comprising (a) forming a benzylthioether-linked solid support-bound thiol compound, said thiol compound having at least one functional group for generating at least one peptide bond; (b) coupling to said thiol compound at least one protected amino acid or peptide to form a peptide of desired amino acid sequence; and (c) cleaving the peptide from the support at the benzylthioether linkage.
Claim 2
Dependent Claim
69 words
In a method of synthesizing sulfhydryl-containing peptides, the improvement comprising (a) forming a benzylthioether-linked solid support-bound thiol compound, said thiol compound having at least one functional group for generating at least one peptide bond; (b) coupling to said thiol compound at least one protected amino acid or peptide to form a peptide of desired amino acid sequence; and (c) cleaving the peptide from the support at the benzylthioether linkage.
Claim 3
Dependent Claim
145 words
In a method of synthesizing sulfhydryl-containing peptides, the improvement comprising (a) forming a benzylhioether-linked solid support-bound thiol compound with the general formula ##STR13## wherein X is H, NH 2 , ##STR14## or acyl-NH, said acyl being an amino acid or a peptide; Y is H, COOH, CONHNH 2 , ##STR15## the ester COOR 1 in which R 1 is selected from the group consisting of methyl, ethyl, phenyl, ortho-nitrophenyl and para-nitrophenyl, the amide CONH 2 , or the amide CONHR 2 in which R 2 is an amino acid or peptide; and providing that X and Y cannot both be H; (b) coupling to said compound at least one protected amino acid or peptide to form the desired peptide sequence; and (c) cleaving the benzylthioether bond to liberate the synthesized peptide from the resin with concomittant regeneration of the free sulfhydryl group in the peptide.
Claim 4
Dependent Claim
145 words
In a method of synthesizing sulfhydryl-containing peptides, the improvement comprising (a) forming a benzylhioether-linked solid support-bound thiol compound with the general formula ##STR13## wherein X is H, NH 2 , ##STR14## or acyl-NH, said acyl being an amino acid or a peptide; Y is H, COOH, CONHNH 2 , ##STR15## the ester COOR 1 in which R 1 is selected from the group consisting of methyl, ethyl, phenyl, ortho-nitrophenyl and para-nitrophenyl, the amide CONH 2 , or the amide CONHR 2 in which R 2 is an amino acid or peptide; and providing that X and Y cannot both be H; (b) coupling to said compound at least one protected amino acid or peptide to form the desired peptide sequence; and (c) cleaving the benzylthioether bond to liberate the synthesized peptide from the resin with concomittant regeneration of the free sulfhydryl group in the peptide.
Claim 5
Dependent Claim
21 words
The method according to claim 1 wherein the synthesized peptide is cyclized by oxidizing sulfhydryl groups to form intramolecular disulfide bonds.
Claim 6
Dependent Claim
26 words
The method according to claim 1 wherein the synthesized peptide is covalently attached to a second peptide by oxidizing sulfhydryl groups to form intermolecular disulfide bonds.
Claim 7
Dependent Claim
73 words
The method according to claim 1 wherein a thioether bond is introduced into the synthesized peptide thus allowing formation of a loop in the peptide, said thioether bond being produced by reacting a sulfhydryl group in the synthesized peptide with an active alkyl group attached to an N.sup.α -moiety or side chain of an amino acid or peptide, said amino acid or peptide being coupled to the synthesized peptide by the thioether bond.
Claim 8
Dependent Claim
17 words
The method according to claim 1 in which the solid support is 1% cross-linked chloromethylated copolystyrene/divinylbenzene resin.
Claim 9
Dependent Claim
14 words
The method according to claim 6 in which the resin-bound thiol compound is ##STR16##
Claim 10
Dependent Claim
14 words
The method according to claim 6 in which the resin-bound thiol compound is ##STR17##
Claim 11
Dependent Claim
14 words
The method according to claim 6 in which the resin-bound thiol compound is ##STR18##
Claim 12
Dependent Claim
88 words
A benzylthioether-linked solid support-bound thiol compound having the formula ##STR19## wherein X is H, NH 2 , ##STR20## or acyl-NHY, said acyl being an amino acid or a peptide; Y is H, COOH, CONHNH 2 , ##STR21## the ester COOR 1 in which R 1 is selected from the group consisting of methyl, ethyl, phenyl, ortho-nitrophenyl and para-nitrophenyl, the amide CONH 2 , or the amide CONHR 2 in which R 2 is an amino acid or peptide; and providing that X and Y cannot both be H.
Claim 13
Dependent Claim
88 words
A benzylthioether-linked solid support-bound thiol compound having the formula ##STR19## wherein X is H, NH 2 , ##STR20## or acyl-NHY, said acyl being an amino acid or a peptide; Y is H, COOH, CONHNH 2 , ##STR21## the ester COOR 1 in which R 1 is selected from the group consisting of methyl, ethyl, phenyl, ortho-nitrophenyl and para-nitrophenyl, the amide CONH 2 , or the amide CONHR 2 in which R 2 is an amino acid or peptide; and providing that X and Y cannot both be H.
Claim 14
Dependent Claim
9 words
A benzylthioether-linked solid support-bound thiol compound of formula ##STR22##
Claim 15
Dependent Claim
9 words
A benzylthioether-linked solid support-bound thiol compound of formula ##STR22##
Claim 16
Dependent Claim
9 words
A benzylthioether-linked solid support-bound thiol compound of formula ##STR23##
Claim 17
Dependent Claim
9 words
A benzylthioether-linked solid support-bound thiol compound of formula ##STR23##
Claim 18
Dependent Claim
9 words
A benzylthioether-linked solid support-bound thiol compound of formula ##STR24##
Claim 19
Dependent Claim
9 words
A benzylthioether-linked solid support-bound thiol compound of formula ##STR24##
Claim 20
Dependent Claim
19 words
A compound according to any of claims 10-13 in which the solid support is 1% cross-linked chloromethylated copolystyrene/divinylbenzene resin.
Claim 21
Dependent Claim
41 words
An antigen comprising a synthesized peptide containing therein a C-terminal cysteamine wherein the C-terminal reactive group of the peptide is a free sulfhydryl group of said cysteamine, said synthesized peptide being conjugatable through the free sulfhydryl group to a carrier protein.
Claim 22
Dependent Claim
41 words
An antigen comprising a synthesized peptide containing therein a C-terminal cysteamine wherein the C-terminal reactive group of the peptide is a free sulfhydryl group of said cysteamine, said synthesized peptide being conjugatable through the free sulfhydryl group to a carrier protein.
Claim 23
Dependent Claim
43 words
An anitgen comprising a synthesized peptide containing therein an N-terminal β-mercaptopropionic acid wherein the N-terminal reactive group of the peptide is a free sulfhydryl group of said β-mercaptopropionic acid, said synthesized peptide being conjugatable through the free sulfhydryl group to a carrier protein.
Claim 24
Dependent Claim
43 words
An anitgen comprising a synthesized peptide containing therein an N-terminal β-mercaptopropionic acid wherein the N-terminal reactive group of the peptide is a free sulfhydryl group of said β-mercaptopropionic acid, said synthesized peptide being conjugatable through the free sulfhydryl group to a carrier protein.
Claim 25
Dependent Claim
61 words
An antibody which specifically binds to an antigen comprising a synthesized peptide containing therein a C-terminal cysteamine wherein the C-terminal reactive group of the peptide is a free sulfydryl group of said cysteamine, said peptide being conjugatable through the free sulfhydryl group to a carrier protein such that upon immunization of a suitable host, the conjugate elicits production of the antibody.
Claim 26
Dependent Claim
61 words
An antibody which specifically binds to an antigen comprising a synthesized peptide containing therein a C-terminal cysteamine wherein the C-terminal reactive group of the peptide is a free sulfydryl group of said cysteamine, said peptide being conjugatable through the free sulfhydryl group to a carrier protein such that upon immunization of a suitable host, the conjugate elicits production of the antibody.
Claim 27
Dependent Claim
64 words
An antibody which specifically binds to an antigen comprising a synthesized peptide containing therein an N-terminal β-mercaptopropionic acid wherein the N-terminal reactive group of the peptide is a free sulfhydryl group of said β-mercaptopropionic acid, said synthesized peptide being conjugatable through the free sulfhydryl group to a carrier protein such that upon immunization of a suitable host, the conjugate elicits production of the antibody.
Claim 28
Dependent Claim
64 words
An antibody which specifically binds to an antigen comprising a synthesized peptide containing therein an N-terminal β-mercaptopropionic acid wherein the N-terminal reactive group of the peptide is a free sulfhydryl group of said β-mercaptopropionic acid, said synthesized peptide being conjugatable through the free sulfhydryl group to a carrier protein such that upon immunization of a suitable host, the conjugate elicits production of the antibody.
Claim 29
Dependent Claim
27 words
A method for synthesizing a peptide according to claim 2, further comprising conjugating the peptide through the free sulfhydryl group of the peptide to a carrier protein.
References Cited (Backward Citations)
US3743628A
Cited
US4193915A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-11-22 | 1992-05-23 | 1992-11-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-11-22 | 1996-05-23 | 1996-11-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-11-22 | 2000-05-23 | 2000-11-22 | $7700.00 | Window Closed / Lapsed |