US5625030A
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Methods for synthesizing oligomers containing hydroxy acid units
Assignee: Yield10 Bioscience Inc
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Filing: 1995-11-20
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Granted: 1997-04-29
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Expires: 2015-11-20
Abstract
Abstract Methods for synthesizing oligomers containing hydroxy acids, and optionally containing other types of monomers or oligomers such as amino acids, carbohydrates, nucleotides and peptides, are provided which are rapid, simple, and readily automated. The oligomers have a C-terminal and an O, S or N-terminal end. The starting hydroxy acid can be covalently bound at either the C-terminal or O, S or N-terminal end to a solid support. The bond to the solid support can be an amide, thioester, ester, phosphate, silyl ether, carbamate, benzyl ether, or other linkage that can be cleaved either chemically or enzymatically.
Inventors
- 👤 Simon F. Williams
- 👤 Oliver P. Peoples
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 07:58
CPC Classifications
C; C07; C07K; C07K1/00; C07K1/04; C07B; C07B41/00; C07B41/12; C07B43/00; C07B43/06; C07K1/047; C07K11/00; C07K11/02
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
234 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises covalently incorporating in place of at least one of the additional hydroxy acid monomers a molecule selected from the group consisting of nucleotides, sugars, thio acids, lipids, steroids, and inorganic molecules, and oligomers thereof, wherein the molecule comprises at least one functional group capable of reacting with at least one terminal group on at least one of the hydroxy acid monomers, thereby to permit the molecule to be covalently incorporated into the oligomer.
Claim 2
Independent Claim
234 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises covalently incorporating in place of at least one of the additional hydroxy acid monomers a molecule selected from the group consisting of nucleotides, sugars, thio acids, lipids, steroids, and inorganic molecules, and oligomers thereof, wherein the molecule comprises at least one functional group capable of reacting with at least one terminal group on at least one of the hydroxy acid monomers, thereby to permit the molecule to be covalently incorporated into the oligomer.
Claim 3
Dependent Claim
30 words
The method of claim 1 further comprising protecting the functional side groups on the monomers prior to preparing the oligomer, and deprotecting the protected side groups after preparing the oligomer.
Claim 4
Dependent Claim
15 words
The method of claim 1 further comprising cleaving the first monomer from the solid support.
Claim 5
Dependent Claim
12 words
The method of claim 2 wherein the protecting group is deprotected chemically.
Claim 6
Dependent Claim
12 words
The method of claim 2 wherein the protecting group is deprotected enzymatically.
Claim 7
Dependent Claim
20 words
The method of claim 1 further comprising activating the terminal carboxylic group prior to reaction with the terminal hydroxyl group.
Claim 8
Dependent Claim
10 words
The method of claim 1 wherein the process is automated.
Claim 9
Independent Claim
230 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises incorporating a sugar in place of at least one of the additional hydroxy acid monomers by the steps of i) selecting a sugar to be incorporated into the oligomer; ii) selectively protecting all but one of the reactive hydroxy groups on the sugar; iii) reacting the unprotected reactive hydroxy group to form a carboxyl derivative; and iv) reacting the carboxyl derivative with an unprotected --OH group on the oligomer.
Claim 10
Independent Claim
230 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises incorporating a sugar in place of at least one of the additional hydroxy acid monomers by the steps of i) selecting a sugar to be incorporated into the oligomer; ii) selectively protecting all but one of the reactive hydroxy groups on the sugar; iii) reacting the unprotected reactive hydroxy group to form a carboxyl derivative; and iv) reacting the carboxyl derivative with an unprotected --OH group on the oligomer.
Claim 11
Dependent Claim
15 words
The method of claim 1 wherein the molecule is a nucleotide or oligomer of nucleotides.
Claim 12
Dependent Claim
26 words
The method of claim 1 further comprising incorporating an amino acid or oligomer thereof into the oligomer in place of at least one hydroxy acid monomer.
Claim 13
Independent Claim
182 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises incorporating a plurality of amino acids into the oligomer in place of at least one of the additional hydroxy acid monomers.
Claim 14
Independent Claim
182 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises incorporating a plurality of amino acids into the oligomer in place of at least one of the additional hydroxy acid monomers.
Claim 15
Dependent Claim
19 words
The method of claim 11 wherein at least one of the amino acids incorporated is an amino acid oligomer.
Claim 16
Independent Claim
201 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, wherein the hydroxy acid monomer selected from the group consisting of 3-, 4- and 5- hydroxy acid monomers, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises incorporating an amino acid or oligomer thereof into the oligomer in place of at least one of the additional hydroxy acid monomers.
Claim 17
Independent Claim
201 words
A method for preparing oligomers of hydroxy acids comprising the steps of a) selecting a first hydroxy acid monomer, wherein the hydroxy acid monomer selected from the group consisting of 3-, 4- and 5- hydroxy acid monomers, b) linking the first hydroxy acid monomer to a solid support via either the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer, c) selecting a second hydroxy acid monomer, d) protecting the terminal group on the second hydroxy acid monomer opposite to the terminal group linked to the solid support in step b, e) linking the first monomer and the second monomer through the unprotected terminal groups to form an oligomer bound to a solid support, f) deprotecting the protected terminal group of the second monomer, g) selecting additional hydroxy acid monomers, h) protecting either the terminal carboxy group or the terminal hydroxy group on the additional monomers as necessary to link the additional monomers to the deprotected terminal group, and i) linking the additional monomers to the oligomer, wherein the method further comprises incorporating an amino acid or oligomer thereof into the oligomer in place of at least one of the additional hydroxy acid monomers.
Claim 18
Dependent Claim
13 words
The method of claim 12 wherein the amino acid oligomer is a peptide.
Claim 19
Dependent Claim
13 words
The method of claim 13 wherein the amino acid oligomer is a peptide.
Claim 20
Dependent Claim
28 words
The method of claim 1 further comprising preparing a plurality of different hydroxy oligomers each comprising a different molecule incorporated therein, and screening the oligomers for biological activity.
Claim 21
Dependent Claim
37 words
The method of claim 11 further comprising preparing a plurality of different hydroxy acid oligomers each comprising a different amino acid or oligomer thereof incorporated in the hydroxy acid oligomer, and screening the oligomers for biological activity.
Claim 22
Dependent Claim
33 words
The method of claim 1 wherein the terminal carboxy group on the first monomer or the terminal hydroxy group on the first monomer is linked to the solid support via a protecting group.
Claim 23
Dependent Claim
25 words
The method of claim 1 wherein the molecule comprises at least one functional group selected from the group consisting of hydroxy, carboxy, thio and amine.
Claim 24
Dependent Claim
27 words
The method of claim 19 wherein the molecule comprises first and second functional groups and at least one of the functional groups is protected prior to incorporation.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-04-28 | 2000-10-28 | 2001-04-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-04-28 | 2004-10-28 | 2005-04-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-04-28 | 2008-10-28 | 2009-04-29 | $7700.00 | Window Closed / Lapsed |