EP0113452A2
Expired / Lapsed
EP
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Magnetic particles as supports for organic synthesis
Assignee: Genetics Institute LLC
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Filing: 1983-12-12
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Granted: —
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Expires: 2003-12-12
Abstract
Abstract A support system for organic synthesis comprising magnetic particles in a dispersion medium covalently attached to functional groups having affinity for polymer subunits, and methods for making and using the support system, e.g. for synthesis of oligodeoxynucleotides and polypeptides.
Inventors
- 👤 Steven A. Benner
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-03 23:16
CPC Classifications
C; C07; C07H; C07H21/00; B; B03; B03C; B03C1/00; B03C1/005; B03C1/01; C07K; C07K1/00; C07K1/04; C07K1/042; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/582
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
23 words
Oligomer synthesis support comprising a magnetic particle covalently bound to oligomer subunits, said oligomer subunits comprising subunits of deoxyribonucleic acid or ribonucleic acid.
Claim 2
Dependent Claim
23 words
Oligomer synthesis support comprising a magnetic particle covalently bound to oligomer subunits, said oligomer subunits comprising subunits of deoxyribonucleic acid or ribonucleic acid.
Claim 3
Dependent Claim
14 words
The composition of claim 1, wherein said oligomer subunits comprise subunits of deoxyribonucleic acid.
Claim 4
Dependent Claim
11 words
The composition of claim 1, wherein said magnetic particles comprise magnetite.
Claim 5
Dependent Claim
11 words
The composition of claim 1, wherein said magnetic particles are non-porous.
Claim 6
Dependent Claim
19 words
The composition of claim 1, wherein said oligomer synthesis support exists as a colloidal suspension in a dispersion medium.
Claim 7
Dependent Claim
12 words
The composition of claim 1, wherein said magnetic particles are single domain.
Claim 8
Dependent Claim
19 words
The composition of claim 1, wherein the size of said magnetic particles is in the range of 10-100,000 Angstroms.
Claim 9
Dependent Claim
29 words
An organic synthesis support that comprises a magnetic particle having reactive sites covalently coupled to functional groups, the remaining reactive sites being blocked against reaction by silyl blocking groups.
Claim 10
Dependent Claim
29 words
An organic synthesis support that comprises a magnetic particle having reactive sites covalently coupled to functional groups, the remaining reactive sites being blocked against reaction by silyl blocking groups.
Claim 11
Dependent Claim
11 words
The composition of claim 8, wherein said magnetic particles comprise magnetite.
Claim 12
Dependent Claim
11 words
The composition of claim 8, wherein said magnetic particles are non-porous.
Claim 13
Dependent Claim
18 words
The composition of claim 8, wherein said maometic particles exist as a colloidal suspension in a dispersion medium.
Claim 14
Dependent Claim
12 words
The composition of claim 8, wherein said magnetic particles are single domain.
Claim 15
Dependent Claim
16 words
The composition of claim 8, wherein said magnetic particles are in the range of 10-100,000 Angstroms.
Claim 16
Dependent Claim
16 words
The composition of claim 8, wherein said magnetic particles are in the range of 10-10,000 Angstroms.
Claim 17
Dependent Claim
14 words
The composition of claim 8, wherein said functional groups are amino, carboxyl, or hydroxyl.
Claim 18
Dependent Claim
82 words
The composition of claim 8, wherein the reactive sites are blocked by reaction with a compound having the following structure: wherein Si is the silicon of an organosilane; X is a leaving group and member of the group alkoxy, halogen or aamine; n is an integer having a value of 1 or 2; R is a member of a group of alkyl, alkenyl, alkynyl or aryl where the group contains at least one carbon atom and does not contain any reactive functionality.
Claim 19
Dependent Claim
12 words
The composition of claim 8, wherein said silyl blocking agent is trimethysilylchloride.
Claim 20
Dependent Claim
141 words
An oligomer synthesis support having the following structure: wherein M is the surface of a magnetic support particle; 0 is the oxygen of the metal oxide or hydroxide; Si is the silicon of the organosilane linking or coupling agent; X is a member of the group of alkenyloxy, alkaryloxy, alkynyloxy, alkoxy and halo; n is an integer with a value of 0, 1 or 2; R is a linking group and member of a group of alkyl, alkenyl, alkynyl or aryl where the group contains more than one carbon atom; m is an integer with a value of 1, 2 or 3; Y is a member of the group of amino, hydroxyl or carboxyl which will covalently combine with an oligomer subunit or precursor; p is an integer with a value of at least 1; Z is an initial oligomer subunit.
Claim 21
Dependent Claim
141 words
An oligomer synthesis support having the following structure: wherein M is the surface of a magnetic support particle; 0 is the oxygen of the metal oxide or hydroxide; Si is the silicon of the organosilane linking or coupling agent; X is a member of the group of alkenyloxy, alkaryloxy, alkynyloxy, alkoxy and halo; n is an integer with a value of 0, 1 or 2; R is a linking group and member of a group of alkyl, alkenyl, alkynyl or aryl where the group contains more than one carbon atom; m is an integer with a value of 1, 2 or 3; Y is a member of the group of amino, hydroxyl or carboxyl which will covalently combine with an oligomer subunit or precursor; p is an integer with a value of at least 1; Z is an initial oligomer subunit.
Claim 22
Dependent Claim
13 words
The composition of claim 18 or 46, wherein said linking group is polymethylene.
Claim 23
Dependent Claim
13 words
The composition of claim 18 or 46, wherein said amino group is N-trimethylene-carboxamido-dimethylene.
Claim 24
Dependent Claim
20 words
The composition of claim 18 or 46, wherein said member Z is a deoxyribonucleic acid, ribonucleic acid or polypeptide subunit.
Claim 25
Independent Claim
31 words
A method of making a support for organic synthesis that comprises reacting a magnetic particle with a silane coupling or linking agent and reacting the resulting product with an oligomer subunit.
Claim 26
Independent Claim
31 words
A method of making a support for organic synthesis that comprises reacting a magnetic particle with a silane coupling or linking agent and reacting the resulting product with an oligomer subunit.
Claim 27
Dependent Claim
40 words
The method of claim 22, wherein the silane coupling or linking agent has a silicon portion and an organic portion, the magnetic particle is covalently attached to said silicon portion and said oligomer subunit is reacted with the organic portion.
Claim 28
Dependent Claim
11 words
The method of claim 22, wherein said magnetic particles comprise magnetite.
Claim 29
Dependent Claim
11 words
The method of claim 22, wherein said magnetic particles are non-porous.
Claim 30
Dependent Claim
115 words
The method of claim 22, wherein said silane coupling or linking agent has the formula: Si(X) n [R m (Y) p l 4-n where Si is the silicon of the organosilane linking or coupling agent; X is a member of the group of alkyloxy, alkenyloxy, alkynyloxy, alkaryloxy, aryloxy, and halo; R is a member of the group of alkyl, alkenyl, alkynyl, aryl, alkaryl, or aralkyl; m is an integer having a value of at least one; p is an integer with a value of at least one; Y is a functional group of the group amino, carboxyl or hydroxy, which can react with an oligomer subunit; n is an integer having a value of 1-3.
Claim 31
Independent Claim
42 words
The method of making magnetic particles comprising (a) producing a ferrous formate aerosal (b) drying said aerosol in a stream of heated ambient air at 180° to 220°C to produce particles of ferrous formate (c) pyrolyzing said particles in an inert atmosphere.
Claim 32
Independent Claim
42 words
The method of making magnetic particles comprising (a) producing a ferrous formate aerosal (b) drying said aerosol in a stream of heated ambient air at 180° to 220°C to produce particles of ferrous formate (c) pyrolyzing said particles in an inert atmosphere.
Claim 33
Dependent Claim
12 words
The composition of claim 27, wherein said magnetic particles are single domain.
Claim 34
Dependent Claim
16 words
The composition of claim 27, wherein said magnetic particles are in the range of 10-100,000 Angstroms.
Claim 35
Dependent Claim
16 words
The composition of claim 27, wherein said magnetic particles are in the range of 10-10,000 Angstroms.
Claim 36
Dependent Claim
23 words
The method of claim 27 wherein the size of said magnetic particle is controlled by controlling the concentration of the ferrous formate solution.
Claim 37
Independent Claim
46 words
A method for synthesizing oligomers that comprises: (a) supporting an initial oligomer subunit(s) on magnetic particles (b) reacting an oligomer subunit with said initial oligomer subunit (c) and forming an oligomer product by sequentially repeating the attachment of oligomer subunits until the desired product is synthesized
Claim 38
Independent Claim
46 words
A method for synthesizing oligomers that comprises: (a) supporting an initial oligomer subunit(s) on magnetic particles (b) reacting an oligomer subunit with said initial oligomer subunit (c) and forming an oligomer product by sequentially repeating the attachment of oligomer subunits until the desired product is synthesized
Claim 39
Dependent Claim
13 words
The method of claim 32, wherein the oligomer synthesis support particle comprises magnetite.
Claim 40
Dependent Claim
18 words
The method of claim 32, wherein said oligomer subunits comprise subunits of deoxyribonucleic acid, ribonucleic acid or polypeptides.
Claim 41
Dependent Claim
11 words
The method of claim 32, wherein said magnetic particles comprise magnetite.
Claim 42
Dependent Claim
11 words
The method of claim 32, wherein said magnetic particles are non-porous.
Claim 43
Dependent Claim
12 words
The method of claim 32, wherein said magnetic particles are single domain.
Claim 44
Dependent Claim
16 words
The method of claim 32, wherein said magnetic particles are in the range of 10-100,000 Angstroms.
Claim 45
Dependent Claim
16 words
The method of claim 32, wherein said magnetic particles are in the range of 10-10,000 Angstroms.
Claim 46
Dependent Claim
20 words
The method of claim 32, further comprising maintaining maqnetic particles in a colloidal suspension in a dispersion medium during synthesis.
Claim 47
Dependent Claim
56 words
An oligomer synthesis kit having component materials capable of being reacted together to synthesize an oligomer, comprising magnetic particles covalently bound to a functional croup which is reactive to form a covalent bond with an oligomer subunit, and a source of oligomer subunits which are capable of chemically reacting with each other to form an oligomer.
Claim 48
Dependent Claim
56 words
An oligomer synthesis kit having component materials capable of being reacted together to synthesize an oligomer, comprising magnetic particles covalently bound to a functional croup which is reactive to form a covalent bond with an oligomer subunit, and a source of oligomer subunits which are capable of chemically reacting with each other to form an oligomer.
Claim 49
Dependent Claim
17 words
The oligomer synthesis kit of claim 41, wherein there are a plurality of sources of oligomer subunits.
Claim 50
Dependent Claim
28 words
The oligomer synthesis kit of claim 42, wherein the plurality of sources of oligomer subunits comprise separate sources of dexoynucleotides containing the nucleosides deoxyadenosine, deoxyguanosine, deoxycytidine and deoxythymidine.
Claim 51
Dependent Claim
26 words
The oligomer synthesis kit of claim 42, wherein the sources of oligomer subunits comprise separate sources of ribonucleotides containing the nucleosides adenosine, guanosine, cytidine and uridine.
Claim 52
Dependent Claim
47 words
The oligomer synthesis kit of claim 42 wherein the sources of oligomer subunits comprise separate sources of amino acids selected from the group of Glycine, L-Alanine, L-Valine, L-Leucine, L-Isoleucine, L-Serine, L-Threonine, L-Tyrosine, L-Phenylalanine, L-Tryptophan, L-Aspartic acid, L-Glutamic acid, L-Lysine, L-Arginine, L-Histidine, L-Asparagine, L-Glutamine, L-Cysteine, L-Methionine and L-Prcline.
Claim 53
Dependent Claim
164 words
An oligomer support synthesis having the following structure: wherein M is the support particle, 0 is the oxygen of the metal oxide or hydroxide, Si is silicon, X is a cleaving group, R is a linking group, Y is a functional group which can react with and bind the oligomer subunit or a group linked thereto, or cross linking agents B and B' which are chemical bonds or functional groups which react to form covalent bonds with the functional group Y, A is a linking group wich bridges the Y groups and is bound to the oligomer subunit to be worked on, either directly or through reactive group C, n is an integer having a value of 1 to 3, m is an integer having a value of at least 1, p is an integer having a value of 1-3, q and r are integers having the value of at least 1, q + r being from 3-7, and s is 0 to 5.
Claim 54
Dependent Claim
164 words
An oligomer support synthesis having the following structure: wherein M is the support particle, 0 is the oxygen of the metal oxide or hydroxide, Si is silicon, X is a cleaving group, R is a linking group, Y is a functional group which can react with and bind the oligomer subunit or a group linked thereto, or cross linking agents B and B' which are chemical bonds or functional groups which react to form covalent bonds with the functional group Y, A is a linking group wich bridges the Y groups and is bound to the oligomer subunit to be worked on, either directly or through reactive group C, n is an integer having a value of 1 to 3, m is an integer having a value of at least 1, p is an integer having a value of 1-3, q and r are integers having the value of at least 1, q + r being from 3-7, and s is 0 to 5.
Claim 55
Dependent Claim
8 words
The support of claim 46, having the structure:
Claim 56
Dependent Claim
19 words
The support of claim 47, wherein C is -CO(CH 2 ) 2 Co-; and Z is a deoxyribonucleotide subunit.
References Cited (Backward Citations)
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