Using internal marker

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.

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.

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.

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.

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.sub.2).sub.a --Z and --(CH.sub.2).sub.a --NH--Z wherein a is 0 or a positive integer and Z is selected from the group consisting of:
• ##STR58##

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.

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.

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.

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.

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.

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.