Patent US4755558A successfully refreshed from Google Patents.
US4755558A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Using internal marker
Assignee: Beckman Coulter Inc
•
Filing: 1986-05-30
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Granted: 1988-07-05
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Expires: 2006-05-30
Abstract
Abstract A method is provided for quantitatively monitoring the deprotection and coupling reactions employed in the solid phase synthesis of peptides. The method entails synthesizing a peptide on a support matrix that has a first marker associated therewith. The amino acids employed in the peptide synthesis procedure have a second marker attached thereto, which can be the blocking group used for the amino acid. After the coupling or deprotection step a portion of the support matrix is processed to release first and second identifers from the first and second markers, respectively. The completeness of the coupling or deprotection step can be determined by comparing the relative amounts of the detected first and second identifiers. Novel compositions of matter are used in or produced during this method, including support matrixes having pyrolyzable markers attached thereto.
Inventors
- 👤 Suresh M. Kalbag
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 18:07
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/10; C07K5/1002; C07K5/1005; C07K5/1008; C07C; C07C271/00; C07C271/06; C07C271/08; C07C271/10; C07C271/22; C07K1/00; C07K1/04; C07K1/042; C07K1/06; C07K1/061; C07K1/063; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/28
Claims Analysis
Total Claims: 78
Claim 1
Independent Claim
108 words
A composition of matter comprising a peptide supported by a support matrix, the peptide having a terminal amino acid with an N-terminus blocking group attached thereto, the support matrix having a marker attached thereto, wherein: (a) the composition can be treated without deleteriously affecting the marker or the peptide to release the N-terminus blocking group for making the terminal amino acid available to react with another N-terminus blocked amino acid to lengthen the peptide; and (b) the composition can be processed without deleteriously affecting the peptide to release a first detectable identifier from the marker and a second detectable identifier from the blocking group, the identifiers being different.
Claim 2
Dependent Claim
108 words
A composition of matter comprising a peptide supported by a support matrix, the peptide having a terminal amino acid with an N-terminus blocking group attached thereto, the support matrix having a marker attached thereto, wherein: (a) the composition can be treated without deleteriously affecting the marker or the peptide to release the N-terminus blocking group for making the terminal amino acid available to react with another N-terminus blocked amino acid to lengthen the peptide; and (b) the composition can be processed without deleteriously affecting the peptide to release a first detectable identifier from the marker and a second detectable identifier from the blocking group, the identifiers being different.
Claim 3
Dependent Claim
16 words
The composition of claim 1 comprising at least two such peptides supported by the support matrix.
Claim 4
Dependent Claim
15 words
The composition of claim 1 having a plurality of markers attached to the support matrix.
Claim 5
Dependent Claim
35 words
The composition of claim 1 wherein the N-terminus blocking group is selected from the group consisting of t-butyloxycarbonyl, 2-(4-biphenylyl)-2-propyloxy carbonyl, alpha-2,4,5,-tetramethylbenzyloxy carbonyl, 2-phenyl-2-propyloxycarbonyl, 2-(3,5-dimethoxyphenyl)-2-propyloxy carbonyl, fluorenyl methyloxy carbonyl, 3-nitro-2-pyridine sulfenyl, and homologs and analogs thereof.
Claim 6
Dependent Claim
29 words
The composition of claim 1 wherein the support matrix is selected from the group consisting of styrene and divinylbenzene copolymers, polymethylmethacrylate, polysaccharides, phenolic resins, silica, porous glass, and polyacrylamides.
Claim 7
Dependent Claim
137 words
A composition of matter comprising at least one peptide supported by a support matrix, each peptide having a terminal amino acid, the composition having the formula: ##STR43## where: R is the support matrix; m and n are integers of at least 1; X is a side chain comprising the marker; L is a linking group; Y is an amino acid; AA is the terminal amino acid of the peptide; and NTBG is an N-terminus blocking group; wherein the N-terminus blocking group can be removed from the composition, without deleteriously affecting the marker or the peptide, for making AA available for reacting with another amino acid to lengthen the peptide, and the composition can be processed to release first and second detectable identifiers from the marker and NTBG, respectively, the identifiers being different, without delteriously affecting the peptide.
Claim 8
Dependent Claim
137 words
A composition of matter comprising at least one peptide supported by a support matrix, each peptide having a terminal amino acid, the composition having the formula: ##STR43## where: R is the support matrix; m and n are integers of at least 1; X is a side chain comprising the marker; L is a linking group; Y is an amino acid; AA is the terminal amino acid of the peptide; and NTBG is an N-terminus blocking group; wherein the N-terminus blocking group can be removed from the composition, without deleteriously affecting the marker or the peptide, for making AA available for reacting with another amino acid to lengthen the peptide, and the composition can be processed to release first and second detectable identifiers from the marker and NTBG, respectively, the identifiers being different, without delteriously affecting the peptide.
Claim 9
Dependent Claim
27 words
The composition of claim 6 wherein X is --(CH.sub.2).sub.a --(NH).sub.q --Z where a is 0 or a positive integer; q=0 or 1; and Z is the marker.
Claim 10
Dependent Claim
37 words
The composition of claim 7 where Z is ##STR44## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 11
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR45## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 12
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR46## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 13
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR47## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 14
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR48## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 15
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR49## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 16
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR50## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 17
Dependent Claim
37 words
The composition of claim 7 wherein Z is ##STR51## and wherein the composition can be processed by being pyrolyzed to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 18
Dependent Claim
41 words
The composition of claim 6 wherein X is selected from the group consisting of ##STR52## wherein: a is 0 or a positive integer; and Z is selected from the group consisting of --O--trityl; --S--trityl, --O--pityl, --S--pityl; and homologs and analogs thereof.
Claim 19
Dependent Claim
21 words
The composition of claim 16 wherein NTBG is selected from the group consisting of fluorenyl methyloxy carbonyl and 3-nitro-pyridine sulfenyl groups.
Claim 20
Dependent Claim
21 words
The composition of claim 6 wherein L is selected from the group consisting of ##STR53## wherein b is 0 or 1.
Claim 21
Dependent Claim
46 words
A composition of matter having the formula: ##STR54## where R is a support matrix; Y is an amino acid; m and n are integers of at least 1; AA is an amino acid; L is a linking group; and a is 0 or a positive integer.
Claim 22
Dependent Claim
46 words
A composition of matter having the formula: ##STR54## where R is a support matrix; Y is an amino acid; m and n are integers of at least 1; AA is an amino acid; L is a linking group; and a is 0 or a positive integer.
Claim 23
Dependent Claim
46 words
A composition of matter having the formula: ##STR55## where R is a support matrix; Y is an amino acid; m and n are integers of at least 1; AA is an amino acid; L is a linking group; and a is 0 or a positive integer.
Claim 24
Dependent Claim
46 words
A composition of matter having the formula: ##STR55## where R is a support matrix; Y is an amino acid; m and n are integers of at least 1; AA is an amino acid; L is a linking group; and a is 0 or a positive integer.
Claim 25
Dependent Claim
200 words
A composition of matter comprising at least one peptide attached to a support matrix, each peptide having a terminal amino acid, the composition having the formula ##STR56## wherein: (a) R is the support matrix; (b) m and n are integers of at least 1; (c) X is a side chain comprising the marker; (d) L is a linking group; (e) Y is an amino acid; (f) AA is the terminal amino acid of the peptide; (g) the terminal amino acid is available to react with an N-terminus blocked amino acid to produce a lengthened peptide having a new terminal amino acid, the N-terminus blocked amino acid having an N-terminus blocking group attached thereto; (h) the lengthened peptide attached to the support matrix can be treated to release the N-terminus blocking group, without deleteriously affecting the marker or the peptide, so that the terminal amino acid is available to react with another N-terminus blocked amino acid to further lengthen the peptide; and (i) the lengthened peptide attached to the support matrix can be processed without deleteriously affecting the peptide to release a first detectable identifier from the marker and a second detectable identifier from the blocking group, the identifiers being different.
Claim 26
Dependent Claim
200 words
A composition of matter comprising at least one peptide attached to a support matrix, each peptide having a terminal amino acid, the composition having the formula ##STR56## wherein: (a) R is the support matrix; (b) m and n are integers of at least 1; (c) X is a side chain comprising the marker; (d) L is a linking group; (e) Y is an amino acid; (f) AA is the terminal amino acid of the peptide; (g) the terminal amino acid is available to react with an N-terminus blocked amino acid to produce a lengthened peptide having a new terminal amino acid, the N-terminus blocked amino acid having an N-terminus blocking group attached thereto; (h) the lengthened peptide attached to the support matrix can be treated to release the N-terminus blocking group, without deleteriously affecting the marker or the peptide, so that the terminal amino acid is available to react with another N-terminus blocked amino acid to further lengthen the peptide; and (i) the lengthened peptide attached to the support matrix can be processed without deleteriously affecting the peptide to release a first detectable identifier from the marker and a second detectable identifier from the blocking group, the identifiers being different.
Claim 27
Dependent Claim
64 words
A composition of matter having the formula: ##STR57## where: R is a support matrix; m is a positive integer; Q is H or a linking group and X is selected from the group consisting of --(CH 2 ) a --Z and --(CH 2 ) a --NH--Z wherein a is 0 or a positive integer and Z is selected from the group consisting of: ##STR58##
Claim 28
Dependent Claim
64 words
A composition of matter having the formula: ##STR57## where: R is a support matrix; m is a positive integer; Q is H or a linking group and X is selected from the group consisting of --(CH 2 ) a --Z and --(CH 2 ) a --NH--Z wherein a is 0 or a positive integer and Z is selected from the group consisting of: ##STR58##
Claim 29
Dependent Claim
9 words
The composition of claim 22 wherein Z is: ##STR59##
Claim 30
Dependent Claim
60 words
A composition of matter having the formula ##STR60## wherein: R is a support matrix; m is a positive integer; Q is H or a linking group; X is selected from the group consisting of ##STR61## a is 0 or a positive integer; and Z is selected from the group consisting of: --O-trityl, --S-trityl, --O-pixyl, --S-pixyl, and homologs and analogs thereof.
Claim 31
Dependent Claim
60 words
A composition of matter having the formula ##STR60## wherein: R is a support matrix; m is a positive integer; Q is H or a linking group; X is selected from the group consisting of ##STR61## a is 0 or a positive integer; and Z is selected from the group consisting of: --O-trityl, --S-trityl, --O-pixyl, --S-pixyl, and homologs and analogs thereof.
Claim 32
Independent Claim
230 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having the formula ##STR62## wherein: (i) R is a support matrix; (ii) m is an integer of at least 1; (iii) X is a side chain having a marker attached thereto; (iv) L is a linking group that is capable of bonding to an amino acid; and (v) the support matrix can be processed to release a first detectable identifier from the marker; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported blocked amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other, and wherein the supported blocked amino acid can be treated to release the N-terminus blocking group without deleteriously affecting the marker to form support matrices having an N-terminus unprotected amino acid attached thereto for reacting with another amino acid; (c) processing at least a portion of the supported blocked amino acid to release the first and second identifiers; and (d) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether the support matrices have any groups which are uncoupled.
Claim 33
Independent Claim
230 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having the formula ##STR62## wherein: (i) R is a support matrix; (ii) m is an integer of at least 1; (iii) X is a side chain having a marker attached thereto; (iv) L is a linking group that is capable of bonding to an amino acid; and (v) the support matrix can be processed to release a first detectable identifier from the marker; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported blocked amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other, and wherein the supported blocked amino acid can be treated to release the N-terminus blocking group without deleteriously affecting the marker to form support matrices having an N-terminus unprotected amino acid attached thereto for reacting with another amino acid; (c) processing at least a portion of the supported blocked amino acid to release the first and second identifiers; and (d) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether the support matrices have any groups which are uncoupled.
Claim 34
Dependent Claim
14 words
The method of claim 25 wherein the N-terminus blocking group releases the second identifier.
Claim 35
Dependent Claim
60 words
The method of claim 26 wherein only a portion of the supported amino acid is processed, the method comprising the additional step of: (e) treating at least a portion of the remainder of the supported blocked amino acid to remove the N-terminus blocking group from the supported amino acid without deleteriously affecting the marker for unblocking the supported amino acid.
Claim 36
Dependent Claim
58 words
The method of claim 27 comprising the additional steps of: (f) processing a portion of the unblocked supported amino acid to release the first and second identifiers; and (g) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether any support matrix has an N-terminus protected amino acid attached thereto.
Claim 37
Dependent Claim
25 words
The method of claim 28 comprising the additional step of: (h) reacting another portion of the unblocked supported amino acid with additional blocked amino acid.
Claim 38
Dependent Claim
40 words
The method of claim 27 comprising repeating steps (b) through (d) before step (e) until the comparison indicates that the support matrices are substantially devoid of any group capable of and available to react with an N-terminus blocked amino acid.
Claim 39
Dependent Claim
33 words
The method of claim 29 or 30 comprising repeating steps (e) through (g) before step (h) until the comparison indicates that the support matrices are substantially devoid of any N-terminus protected amino acid.
Claim 40
Dependent Claim
17 words
The method of claim 29 comprising repeating steps (b) through (h) until a desired peptide is formed.
Claim 41
Dependent Claim
17 words
The method of claim 31 comprising repeating steps (b) through (h) until a desired peptide is formed.
Claim 42
Dependent Claim
16 words
The method of claim 25 wherein the step of processing comprises pyrolyzing the supported amino acid.
Claim 43
Dependent Claim
17 words
The method of claim 25 wherein the step of processing comprises chemically processing the supported amino acid.
Claim 44
Dependent Claim
21 words
The method of claim 25 wherein the step of detecting comprises quantitatively determining the amount of the first and second identifiers.
Claim 45
Dependent Claim
20 words
The method of claim 28 in which step (g) comprises quantitatively determining the amount of the first and second identifiers.
Claim 46
Independent Claim
235 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having the formula ##STR63## wherein: (i) R is a support matrix; (ii) m is an integer of at least 1; (iii) X is a side chain having a marker attached thereto; (iv) L is a linking group that is capable of bonding to an amino acid; and (v) the support matrix can be processed to release a first detectable identifier from the marker; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other; (c) treating the N-terminus blocking group to remove the N-terminus blocking group from the supported blocked amino acid without deleteriously affecting the marker for unblocking the supported blocked amino acid; (d) processing a portion of the unblocked supported amino acid to release the first and second identifiers; (e) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether any support matrix has an N-terminus protected amino acid attached thereto; and (f) reacting another portion of the unblocked supported amino acid with additional blocked amino acid.
Claim 47
Independent Claim
235 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having the formula ##STR63## wherein: (i) R is a support matrix; (ii) m is an integer of at least 1; (iii) X is a side chain having a marker attached thereto; (iv) L is a linking group that is capable of bonding to an amino acid; and (v) the support matrix can be processed to release a first detectable identifier from the marker; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other; (c) treating the N-terminus blocking group to remove the N-terminus blocking group from the supported blocked amino acid without deleteriously affecting the marker for unblocking the supported blocked amino acid; (d) processing a portion of the unblocked supported amino acid to release the first and second identifiers; (e) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether any support matrix has an N-terminus protected amino acid attached thereto; and (f) reacting another portion of the unblocked supported amino acid with additional blocked amino acid.
Claim 48
Dependent Claim
31 words
The method of claim 38 comprising repeating steps (c) through (e) before step (f) until the comparison indicates that the support matrices are substantially devoid of any N-terminus protected amino acid.
Claim 49
Dependent Claim
21 words
The method of claim 38 wherein the step of detecting comprised quantitatively determining the amount of the first and second identifiers.
Claim 50
Dependent Claim
66 words
The method of claim 25 wherein the supported blocked amino acid has the formula: ##STR64## where: R is the support matrix; m and n are integers of at least 1; X is the side chain having the marker attached thereto; L is the linking group; Y is an amino acid; AA is the blocked amino acid of the peptide; and NTBG is the N-terminus blocking group.
Claim 51
Dependent Claim
58 words
The method of claim 41 wherein X is --(CH.sub.2).sub.a --(NH).sub.q --Z where a is 0 or a positive integer; q=0 or 1; and Z is the marker, and wherein the step of processing comprising pyrolyzing the supported blocked amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 52
Dependent Claim
39 words
The method of claim 42 where Z is ##STR65## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 53
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR66## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 54
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR67## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 55
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR68## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 56
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR69## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 57
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR70## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 58
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR71## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 59
Dependent Claim
39 words
The method of claim 42 wherein Z is ##STR72## and wherein the step of processing comprising pyrolyzing the supported amino acid to release at least a portion of Z and NTBG as the first and second detectable identifiers, respectively.
Claim 60
Dependent Claim
41 words
The method of claim 42 wherein X is selected from the group consisting of ##STR73## wherein: a is 0 or a positive integer; and Z is selected from the group consisting of --O--trityl; --S--trityl, --O--pityl, --S--pityl; and homologs and analogs thereof.
Claim 61
Dependent Claim
21 words
The method of claim 51 wherein NTBG is selected from the group consisting of fluorenyl methyloxy carbonyl and 3-nitro-pyridine sulfenyl groups.
Claim 62
Dependent Claim
53 words
The method of claim 25 wherein the supported amino acid has the formula: ##STR74## where R is the support matrix; Y is an amino acid; m and n are integers of at least 1; AA is the blocked amino acid; L is a linking group; and a is 0 or a positive integer.
Claim 63
Dependent Claim
53 words
The method of claim 25 wherein the supported amino acid has the formula: ##STR75## where R is the support matrix; Y is an amino acid; m and n are integers of at least 1; AA is the blocked amino acid; L is a linking group; and a is 0 or a positive integer.
Claim 64
Dependent Claim
23 words
The composition of claim 6 wherein the marker has the formula ##STR76## and the beta carbon has at least one hydrogen attached thereto.
Claim 65
Dependent Claim
14 words
The composition of claim 55 wherein the marker has more than one beta carbon.
Claim 66
Dependent Claim
26 words
The method of claim 25, 34, or 38 wherein the marker has the formula ##STR77## and the beta carbon has at least one hydrogen attached thereto.
Claim 67
Dependent Claim
14 words
The method of claim 57 wherein the marker has more than one beta carbon.
Claim 68
Dependent Claim
153 words
A composition of matter comprising a peptide attached to a support matrix, the peptide having a terminal amino acid, the support matrix having a marker attached thereto, wherein: (a) the terminal amino acid is available to react with an N-terminus blocked amino acid to produce a lengthened peptide having a new terminal amino acid, the N-terminus blocked amino acid having an N-terminus blocking group attached thereto; (b) the lengthened peptide attached to the support matrix can be treated to release the N-terminus blocking group, without deleteriously affecting the marker or the peptide, so that the terminal amino acid is available to react with another N-terminus blocked amino acid to further lengthen the peptide; and (c) the lengthened peptide attached to the support matrix can be processed without deleteriously affecting the peptide to release a first detectable identifier from the marker and a second detectable identifier from the blocking group, the identifiers being different.
Claim 69
Dependent Claim
153 words
A composition of matter comprising a peptide attached to a support matrix, the peptide having a terminal amino acid, the support matrix having a marker attached thereto, wherein: (a) the terminal amino acid is available to react with an N-terminus blocked amino acid to produce a lengthened peptide having a new terminal amino acid, the N-terminus blocked amino acid having an N-terminus blocking group attached thereto; (b) the lengthened peptide attached to the support matrix can be treated to release the N-terminus blocking group, without deleteriously affecting the marker or the peptide, so that the terminal amino acid is available to react with another N-terminus blocked amino acid to further lengthen the peptide; and (c) the lengthened peptide attached to the support matrix can be processed without deleteriously affecting the peptide to release a first detectable identifier from the marker and a second detectable identifier from the blocking group, the identifiers being different.
Claim 70
Independent Claim
201 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having a marker associated therewith, wherein the support matrix can be processed to release a first detectable identifier from the marker, the support matrix having a group capable of bonding to an amino acid; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported blocked amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other, and wherein the supported blocked amino acid can be treated to release the N-terminus blocking group without deleteriously affecting the marker to form support matrices having an N-terminus unprotected amino acid attached thereto for reaction with another amino acid; (c) processing at least a portion of the supported blocked amino acid to release the first and second identifiers; and (d) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether the support matrices have any groups which are uncoupled.
Claim 71
Independent Claim
201 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having a marker associated therewith, wherein the support matrix can be processed to release a first detectable identifier from the marker, the support matrix having a group capable of bonding to an amino acid; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported blocked amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other, and wherein the supported blocked amino acid can be treated to release the N-terminus blocking group without deleteriously affecting the marker to form support matrices having an N-terminus unprotected amino acid attached thereto for reaction with another amino acid; (c) processing at least a portion of the supported blocked amino acid to release the first and second identifiers; and (d) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether the support matrices have any groups which are uncoupled.
Claim 72
Dependent Claim
14 words
The method of claim 60 wherein the marker is attached to the support matrix.
Claim 73
Dependent Claim
18 words
The method of claim 60 wherein the marker is attached to another matrix blended with the support matrix.
Claim 74
Dependent Claim
22 words
The method of claim 60 wherein the group capable of bonding to an amino acid on the support matrix is a peptide.
Claim 75
Independent Claim
206 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having a marker associated therewith, wherein the support matrix can be processed to release a first detectable identifier from the marker, the support matrix having a group capable of bonding to an amino acid; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other; (c) treating the N-terminus blocking group to remove the N-terminus blocking group from the supported blocked amino acid without deleteriously affecting the marker for unblocking the supported blocked amino acid; (d) processing a portion of the unblocked supported amino acid to release the first and second identifiers; (e) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether any support matrix has an N-terminus protected amino acid attached thereto; and (f) reacting another portion of the unblocked supported amino acid with additional blocked amino acid.
Claim 76
Independent Claim
206 words
A method for synthesizing a peptide comprising the steps of: (a) selecting a support matrix having a marker associated therewith, wherein the support matrix can be processed to release a first detectable identifier from the marker, the support matrix having a group capable of bonding to an amino acid; (b) forming a supported blocked amino acid by reacting a plurality of the support matrices with a blocked amino acid to couple the amino acid to the support matrices, the blocked amino acid having an N-terminus blocking group attached thereto, wherein the supported amino acid can be processed to release a second detectable identifier, the first and second identifiers being different from each other; (c) treating the N-terminus blocking group to remove the N-terminus blocking group from the supported blocked amino acid without deleteriously affecting the marker for unblocking the supported blocked amino acid; (d) processing a portion of the unblocked supported amino acid to release the first and second identifiers; (e) detecting the first and second identifiers and comparing the respective amounts of the detected identifiers for determining whether any support matrix has an N-terminus protected amino acid attached thereto; and (f) reacting another portion of the unblocked supported amino acid with additional blocked amino acid.
Claim 77
Dependent Claim
23 words
The composition of claim 59 wherein the marker has the formula ##STR78## and the beta carbon has at least one hydrogen attached thereto.
Claim 78
Dependent Claim
25 words
The method of claim 60 or 64 wherein the marker has the formula ##STR79## and the beta carbon has at least one hydrogen attached thereto.
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US4582875A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-07-05 | 1992-01-04 | 1992-07-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-07-05 | 1996-01-04 | 1996-07-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-07-05 | 2000-01-04 | 2000-07-05 | $7700.00 | Window Closed / Lapsed |