US5242974A
Expired / Lapsed
US
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Polymer reversal on solid surfaces
Assignee: Affymetrix Inc
•
Filing: 1991-11-22
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Granted: 1993-09-07
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Expires: 2011-11-22
Abstract
Abstract A method for cyclization and reversal of the polarity of polymers on a substrate. The method provides for the formation of a polymer on a substrate (2) with a tether molecule (4). Through unmasking of a protective group (PG2) a cyclic polymer (6) is formed. Through cleavage of an appropriate bond, a polarity reversed polymer (8) is formed. The method finds particular application in the formation of, for example, peptides and oligonucleotides.
Inventors
- 👤 Christopher P. Holmes
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 17:09
CPC Classifications
B; B82; B82Y; B82Y30/00; C; C07; C07H; C07H21/00; C07K; C07K1/00; C07K1/04; C07K1/042; G; G03; G03F; G03F7/00; B01; B01J; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/00351; B01J2219/00427; B01J2219/00432; B01J2219/00497; B01J2219/00527; B01J2219/00529; B01J2219/00583; B01J2219/00585; B01J2219/0059; B01J2219/00596; B01J2219/00603; B01J2219/00605; B01J2219/00608; B01J2219/0061; B01J2219/00612; B01J2219/00614; B01J2219/00617; B01J2219/00623; B01J2219/00626; B01J2219/00659; B01J2219/00709; B01J2219/00711; B01J2219/00718; B01J2219/0072; B01J2219/00722; B01J2219/00725; C07B; C07B2200/00; C07B2200/11; C40; C40B; C40B40/00; C40B40/04; C40B40/06; C40B40/10; C40B60/00; C40B60/14; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
310 words
A method of synthesizing a polymer on a substrate comprising the steps of: a) on a surface of said substrate, having covalently attached thereto a molecule having the general formula: ##STR12## wherein said molecule is selected from the group consisting of: ##STR13## where: X and Y are first and second reactive sites, respectively, X is selected from the group consisting of --O--, --NH--, --S--, --CO 2 --, --S--CH 2 CH 2 O--, and --NHCOCH 2 CH 2 CO 2 --; and Y is selected from the group consisting of --OH, --NH 2 , --SH, --CO 2 H, --S--CH 2 CH 2 OH, and NHCOCH 2 CH 2 CO 2 H, wherein Y is protected with a protective group PG 1 ; T is a tether molecule; PG 1 is a first protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; PG 2 is a second protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; and R and R' are independently selected from the group consisting of hydrogen, methyl, phenyl, and methoxyphenyl; b) covalently coupling a polymer to said reactive site Y by: removing said first protective group PG 1 from said reactive site Y; covalently coupling a monomer to said reactive site Y, said first monomer having a monomer reactive site Y protected with a first protective group PG 1 , wherein said first protective group PG 1 is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; repeating said steps of removing a protective group and coupling a monomer to form a polymer at said reactive site Y; c) removing said second protective group PG 2 ; and d) covalently coupling a region of said polymer to said tether at said first reactive site to form a cyclic polymer.
Claim 2
Independent Claim
310 words
A method of synthesizing a polymer on a substrate comprising the steps of: a) on a surface of said substrate, having covalently attached thereto a molecule having the general formula: ##STR12## wherein said molecule is selected from the group consisting of: ##STR13## where: X and Y are first and second reactive sites, respectively, X is selected from the group consisting of --O--, --NH--, --S--, --CO 2 --, --S--CH 2 CH 2 O--, and --NHCOCH 2 CH 2 CO 2 --; and Y is selected from the group consisting of --OH, --NH 2 , --SH, --CO 2 H, --S--CH 2 CH 2 OH, and NHCOCH 2 CH 2 CO 2 H, wherein Y is protected with a protective group PG 1 ; T is a tether molecule; PG 1 is a first protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; PG 2 is a second protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; and R and R' are independently selected from the group consisting of hydrogen, methyl, phenyl, and methoxyphenyl; b) covalently coupling a polymer to said reactive site Y by: removing said first protective group PG 1 from said reactive site Y; covalently coupling a monomer to said reactive site Y, said first monomer having a monomer reactive site Y protected with a first protective group PG 1 , wherein said first protective group PG 1 is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; repeating said steps of removing a protective group and coupling a monomer to form a polymer at said reactive site Y; c) removing said second protective group PG 2 ; and d) covalently coupling a region of said polymer to said tether at said first reactive site to form a cyclic polymer.
Claim 3
Dependent Claim
27 words
A method as recited in claim 1 further comprising the step of cleaving said bond between T and Y whereby a polarity of said polymer is reversed.
Claim 4
Dependent Claim
22 words
The method as recited in claim 2 wherein said step of cleaving comprises the step of exposing said polymer to an acid.
Claim 5
Dependent Claim
13 words
The method as recited in claim 1 wherein said polymer is a peptide.
Claim 6
Dependent Claim
22 words
The method as recited in claim 4 wherein said polymer is a peptide and said monomer reactive site is an amino group.
Claim 7
Dependent Claim
27 words
The method as recited in claim 5 further comprising the step of cleaving said bond between T and Y whereby a polarity of said peptide is reversed.
Claim 8
Dependent Claim
13 words
The method as recited in claim 1 wherein said polymer is an oligonucleotide.
Claim 9
Dependent Claim
25 words
The method as recited in claim 1 wherein said polymer is an oligonucleotide and said monomer reactive site is a 5' end of said oligonucleotide.
Claim 10
Dependent Claim
27 words
The method as recited in claim 8 further comprising the step of cleaving said bond between T and Y whereby a polarity of said oligonucleotide is reversed.
Claim 11
Dependent Claim
21 words
The method as recited in claim 1 wherein said first protective group is NVOC and said second protective group is FMOC.
Claim 12
Dependent Claim
21 words
The method as recited in claim 1 wherein said first protective group is NVOC and said second protective group is BOC.
Claim 13
Dependent Claim
21 words
The method as recited in claim 1 wherein said first protective group is NVOC and said second protective group is DMT.
Claim 14
Dependent Claim
21 words
The method as recited in claim 1 wherein said first protective group is FMOC and said second protective group is NVOC.
Claim 15
Dependent Claim
21 words
The method as recited in claim 1 wherein said first protective group is DMT and said second protective group is NVOC.
Claim 16
Dependent Claim
27 words
The method as recited in claim 1 wherein said first protective group is NVOC and said second protective group is DMT, and said polymer is an oligonucleotide.
Claim 17
Dependent Claim
47 words
A method as recited in claim 1 wherein said molecule having the general formula: ##STR14## is a molecule having the general formula: ##STR15## where: X and Y are first and second reactive sites, respectively; and PG 1 and PG 2 are first and second protecting groups, respectively.
Claim 18
Dependent Claim
63 words
A method as recited in claim 1 wherein said molecule having the general formula: ##STR16## is a molecule having the general formula: ##STR17## where: X and Y are first and second reactive sites, respectively; PG 1 and PG 2 are first and second protecting groups, respectively; and R and R' are independently selected from the group consisting of hydrogen, methyl, phenyl, and methoxyphenyl.
Claim 19
Dependent Claim
63 words
A method as recited in claim 17 wherein said molecule having the general formula: ##STR18## is a molecule having the general formula: ##STR19## where: X and Y are first and second reactive sites, respectively; PG 1 and PG 2 are first and second protecting groups, respectively; and R and R' are independently selected from the group consisting of hydrogen, methyl, phenyl, and methoxyphenyl.
Claim 20
Dependent Claim
63 words
A method as recited in claim 1 wherein said molecule having the general formula: ##STR20## is a molecule having the general formula: ##STR21## where: X and Y are first and second reactive sites, respectively; PG 1 and PG 2 are first and second protecting groups, respectively; and R and R' are independently selected from the group consisting of hydrogen, methyl, phenyl, and methoxyphenyl.
Claim 21
Dependent Claim
63 words
A method as recited in claim 19 wherein said molecule having the general formula: ##STR22## is a molecule having the general formula: ##STR23## where: X and Y are first and second reactive sites, respectively; PG 1 and PG 2 are first and second protecting groups, respectively; and R and R' are independently selected from the group consisting of hydrogen, methyl, phenyl, and methoxyphenyl.
Claim 22
Dependent Claim
24 words
A method as recited in of claim 1 wherein said first protective group is DMT or BOC and said second protective group is FMOC.
Claim 23
Dependent Claim
42 words
A method as recited in claim 1 wherein said first protective group is selected from the group consisting of DMT, BOC, and FMOC and said second protective group is selected from the group consisting of NVOC, dimethoxybenzyl, dimethoxydimethylbenzyl, α-methylphenoxycinnamates, nitroveratryl, and nitropiperonyl.
Claim 24
Dependent Claim
42 words
A method as recited in claim 1 wherein said first protective group is selected from the group consisting of NVOC, dimethoxybenzyl, dimethoxydimethylbenzyl, α-methylphenoxycinnamates, nitroveratryl, and nitropiperonyl and said second protective group is selected from the group consisting of DMT, BOC, and FMOC.
Claim 25
Independent Claim
250 words
A method of synthesizing an oligopeptide on a substrate comprising the steps of: a) on a surface of said substrate, having covalently attached thereto a molecule having the general formula: ##STR24## where: R and R' are independently selected from the group or hydrogen, C 2 -C 8 alkyl, phenyl, and methoxyphenyl; Y is a reactive site selected from the group consisting of --OH, --NH 2 , --SH, --CO 2 H, --S--CH 2 CH 2 OH, and NHCOCH 2 CH 2 CO 2 H and wherein Y is protected with a protective group PG 1 and; A is oxygen, nitrogen, sulfur, CO, or CO 2 ; n is 1 to 10; PG 1 is a first protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; and PG 2 is a second protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; b) repeating the steps of: 1) removing said protective group PG 1 to provide a first reactive site Y; 2) covalently coupling an amino acid to said first reactive site Y, said first amino acid having said reactive site Y protected with said protective group PG 1 ; to form an oligopeptide at said first reactive site Y; c) removing said protective group PG 2 to provide a second reactive site; and d) covalently coupling a region of said oligopeptide to said substrate bound molecule at said second reactive site to form a cyclic oligopeptide.
Claim 26
Independent Claim
250 words
A method of synthesizing an oligopeptide on a substrate comprising the steps of: a) on a surface of said substrate, having covalently attached thereto a molecule having the general formula: ##STR24## where: R and R' are independently selected from the group or hydrogen, C 2 -C 8 alkyl, phenyl, and methoxyphenyl; Y is a reactive site selected from the group consisting of --OH, --NH 2 , --SH, --CO 2 H, --S--CH 2 CH 2 OH, and NHCOCH 2 CH 2 CO 2 H and wherein Y is protected with a protective group PG 1 and; A is oxygen, nitrogen, sulfur, CO, or CO 2 ; n is 1 to 10; PG 1 is a first protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; and PG 2 is a second protective group and is selected from the group consisting of BOC, FMOC, NVOC, DMT, NV, and FM; b) repeating the steps of: 1) removing said protective group PG 1 to provide a first reactive site Y; 2) covalently coupling an amino acid to said first reactive site Y, said first amino acid having said reactive site Y protected with said protective group PG 1 ; to form an oligopeptide at said first reactive site Y; c) removing said protective group PG 2 to provide a second reactive site; and d) covalently coupling a region of said oligopeptide to said substrate bound molecule at said second reactive site to form a cyclic oligopeptide.
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