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US 5,625,030 AGranted
Methods for synthesizing oligomers containing hydroxy acid units
AssigneeMetabolix, Inc.
InventorsSimon F. Williams, Oliver P. Peoples
Life of this patent
Estimating the term…
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.
Claims20
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.
7 more elements
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.
11 more elements
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.
7 more elements
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.
7 more elements
Dependencies are inferred from the claim text.