Computer-assisted design of anti-peptides based on the amino acid sequence of a target peptide

Claim 1

A method of purifying a target polypeptide or a fragment thereof, comprising (1) designing an anti-peptide sequence having high affinity and specificity for a target peptide or a fragment thereof contained in said polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU12## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU13## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-[poly]peptide comprising the anti-peptide sequence; (3) contacting said synthesized anti-peptide with a sample comprising the target polypeptide to promote binding therebetween; (4) separating said polypeptide-bound anti-peptide from the remaining components in the sample; and (5) separating said peptide from the anti-peptide.

Claim 2

A method of purifying a target polypeptide or a fragment thereof, comprising (1) designing an anti-peptide sequence having high affinity and specificity for a target peptide or a fragment thereof contained in said polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU12## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU13## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-[poly]peptide comprising the anti-peptide sequence; (3) contacting said synthesized anti-peptide with a sample comprising the target polypeptide to promote binding therebetween; (4) separating said polypeptide-bound anti-peptide from the remaining components in the sample; and (5) separating said peptide from the anti-peptide.

Claim 7

A method of preventing proteolysis of a polypeptide in the presence of a proteolytic enzyme, comprising (1) designing an anti-peptide having high affinity and specificity for a target peptide or fragment thereof contained in the polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU14## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU15## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the anti-peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with ##EQU16## wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array a group having a lowest score; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising the anti-peptide sequence; and (3) contacting said anti-polypeptide with a sample comprising the target polypeptide to promote binding therebetween, to thereby protect the polypeptide and prevent the proteolysis thereof when placed in contact with a proteolytic enzyme.

Claim 8

A method of preventing proteolysis of a polypeptide in the presence of a proteolytic enzyme, comprising (1) designing an anti-peptide having high affinity and specificity for a target peptide or fragment thereof contained in the polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU14## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU15## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the anti-peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with ##EQU16## wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array a group having a lowest score; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising the anti-peptide sequence; and (3) contacting said anti-polypeptide with a sample comprising the target polypeptide to promote binding therebetween, to thereby protect the polypeptide and prevent the proteolysis thereof when placed in contact with a proteolytic enzyme.

Claim 12

A method of preventing or reducing the binding of a first polypeptide or fragments thereof having affinity for a target peptide to a second polypeptide comprising said target peptide, comprising 1) designing an anti-peptide sequence having affinity for the target peptide or a fragment thereof by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU17## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,e-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU18## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequence in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising said anti-peptide sequence; and (3) contacting said anti-polypeptide with a sample comprising said second polypeptide to promote binding therebetween to thereby prevent or reduce the binding of said second polypeptide to said first polypeptide in the presence thereof.

Claim 13

A method of preventing or reducing the binding of a first polypeptide or fragments thereof having affinity for a target peptide to a second polypeptide comprising said target peptide, comprising 1) designing an anti-peptide sequence having affinity for the target peptide or a fragment thereof by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU17## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,e-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU18## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequence in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising said anti-peptide sequence; and (3) contacting said anti-polypeptide with a sample comprising said second polypeptide to promote binding therebetween to thereby prevent or reduce the binding of said second polypeptide to said first polypeptide in the presence thereof.

Claim 17

A method of assaying for a target peptide or a fragment thereof, comprising (1) designing an anti-peptide sequence having affinity for a target peptide or a fragment thereof contained in the polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU19## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral of amino acids in the sequence or fragment thereof; n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU20## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the anti-peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (s+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (VIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising the anti-peptide sequence; (3) contacting said anti-polypeptide with a sample comprising the target polypeptide to promote binding; and (4) determining the presence of said polypeptide-bound antipolypeptide.

Claim 18

A method of assaying for a target peptide or a fragment thereof, comprising (1) designing an anti-peptide sequence having affinity for a target peptide or a fragment thereof contained in the polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU19## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral of amino acids in the sequence or fragment thereof; n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3-. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU20## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the anti-peptide sequence or fragment thereof; (XIV) storing said second average hydropathy values in the computer as a seventh array; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (s+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (VIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising the anti-peptide sequence; (3) contacting said anti-polypeptide with a sample comprising the target polypeptide to promote binding; and (4) determining the presence of said polypeptide-bound antipolypeptide.

Claim 26

A method of synthesizing an anti-peptide macromolecule having affinity for a target peptide or a fragment thereof, comprising (1) designing an anti-peptide sequence having high affinity and specificity for a target peptide or a fragment thereof contained in the polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU21## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3 -. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU22## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the anti-peptide sequence or fragment thereof; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising the anti-peptide sequence; (3) covalently binding at least two molecules of said anti-polypeptide to obtain said macromolecule.

Claim 27

A method of synthesizing an anti-peptide macromolecule having affinity for a target peptide or a fragment thereof, comprising (1) designing an anti-peptide sequence having high affinity and specificity for a target peptide or a fragment thereof contained in the polypeptide by (I) obtaining an amino acid sequence P i of the target peptide or a fragment thereof P.sub.i =P.sub.1 -P.sub.2 -P.sub.3 -. . . -P.sub.h ; (II) entering into a computer said amino acid sequence as a first array; (III) obtaining from a first data base a first hydropathic value for each member of the first array h.sub.1 -h.sub.2 -h.sub.3 -. . . -h.sub.n ; (IV) storing within the computer said first hydropathic values as a second array; (V) summing the values in said second array to obtain a value a i for a first moving average hydropathy a i for each member of the first array in accordance with ##EQU21## wherein k is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the sequence or fragment thereof; (VI) storing said values for the first moving average hydropathy in the computer as a third array; (VII) obtaining from a second anti-sense or hydropathically complementary amino acid data base a set comprising at least one anti-sense amino acid per member of the first array; (VIII) storing within the computer said sets of at least one anti-sense amino acid as a fourth array; (IX) generating with the computer at least one anti-sense amino acid sequence by selecting one member Q j ,i per set in the fourth array Q.sub.j,i =Q.sub.j,1 -Q.sub.j,2 -Qj,3 -. . . -Q.sub.j,n' ; (X) storing within the computer said at least one anti-sense amino acid sequence as a fifth array; (XI) obtaining from the first data base a second hydropathic value h j ,i for each member of the fifth array h'.sub.j,i -h'.sub.j,2 -h'.sub.j,3 -. . . -h'.sub.j,n '; (XII) storing within the computer said second hydropathic values as a sixth array; (XIII) summing the values in said sixth array to obtain a value b j ,i for a second moving average hydropathy for each member of the fifth array in accordance with ##EQU22## wherein K is (i-S) to (i+S), i is greater than S and up to or equal to (n-S), j is 1 to the total number of sequences in the fifth array, S is (r-1)/2, r is an odd numeral up to or equal to n, and n is the number of amino acids in the anti-peptide sequence or fragment thereof; (XV) generating within the computer one hydropathic complementary score θ j for each anti-peptide sequence or fragment thereof in the fifth array in accordance with θ.sub.j =((Σ (a.sub.k +b.sub.j,k).sup.2)/(n-2S)).sup.1/2, wherein K is (S+1) to (n-S), and n and S are as defined above; (XVI) storing within the computer the hydropathic complementary scores as an eighth array; (XVII) identifying within the eighth array a group having a lowest score; (XVIII) identifying and selecting the at least one anti-sense sequence in the fifth array which corresponds to said at least one lowest score and identifying it as the at least one anti-peptide sequence having high affinity and selectivity for the target peptide or fragment thereof (2) synthesizing an anti-polypeptide comprising the anti-peptide sequence; (3) covalently binding at least two molecules of said anti-polypeptide to obtain said macromolecule.