Prion-specific peptoid reagents

Abstract

The invention relates to peptoid reagents that interact preferentially with a pathogenic form of a conformational disease protein as compared to a nonpathogenic form of the conformational disease protein where the peptoid reagent comprises an amino-terminal region, a carboxy-terminal region, and at least one peptoid region between the amino-terminal region and the carboxy-terminal region where the peptoid region comprises 3 to about 30 N-substituted glycines, and optionally one or more amino acids. The invention also relates to methods of using the peptoids in detecting and isolating prions, and in the treatment and prevention of prion-related diseases.

1 . A peptoid reagent having a formula of:
   X a -(Q) n -X b      wherein:   each Q is independently an amino acid or an N-substituted glycine, and -(Q) n -defines a peptoid region;   X a  is H, (C 1 -C 6 )alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, (C 1 -C 6 )acyl, amino(C 1-6 )acyl, an amino acid, an amino protecting group, or a polypeptide of 2 to about 100 amino acids, wherein X a  is optionally substituted by a conjugate moiety that is optionally attached through a linker moiety;   X b  is H, (C 1 -C 6 )alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (C 1 -C 6 )alkoxy, aryloxy, aralkoxy, a carboxy protecting group, an amino acid, or a polypeptide of 2 to about 100 amino acids, wherein X b  is optionally substituted by a conjugate moiety that is optionally attached through a linker moiety; and   n is 3 to about 30;   wherein at least about 50% of the peptoid region -(Q) n - comprises N-substituted glycines; and wherein the peptoid region -(Q) n - is designed based on a peptide fragment of a prion protein.   
     
     
         2 . The peptoid reagent of  claim 1  wherein the N-substituted glycine has the formula:
   —(NR—CH 2 —CO)—
 
 where each R is independently selected from (C 2 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )cycloalkyl-aryl, amino(C 1 -C 6 )alkyl, ammonium(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, carboxy, carboxy(C 2 -C 6 )alkyl, carbamyl, carbamyl(C 2 -C 6 )alkyl, guanidino, guanidino(C 1 -C 6 )alkyl, amidino, amidino(C 1 -C 6 )alkyl, thiol, (C 1 -C 6 )alkylthiol, alkylthioalkyl of 2-10 carbon atoms, N-containing heterocyclyl, N-containing heterocyclyl(C 1 -C 6 )alkyl, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolylalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms, and aryl(C 1 -C 6 )alkyl; where each R moiety is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C 1 -C 6 )alkoxy. 
 
     
     
         3 . The peptoid reagent of  claim 1  wherein X b  is an amino acid optionally substituted by a conjugate moiety that is optionally attached through a linker moiety. 
     
     
         4 . The peptoid reagent of  claim 1  wherein n is about 5 to about 15. 
     
     
         5 . The peptoid reagent of  claim 1  wherein each Q is an N-substituted glycine. 
     
     
         6 . The peptoid reagent of  claim 1  wherein the peptoid region -(Q) n - is polyionic at physiologically relevant pH. 
     
     
         7 . The peptoid reagent of  claim 1  wherein the peptoid region -(Q) n - has a net charge of at least 3+ at physiologically relevant pH. 
     
     
         8 . The peptoid reagent of  claim 1  wherein the N-substituted glycine has the formula —(NR—CH 2 —CO)—, wherein R is independently selected from (C 2 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )cycloalkyl-aryl, amino(C 1 -C 6 )alkyl, ammonium(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, carboxy, carboxy(C 2 -C 6 )alkyl, carbamyl, carbamyl(C 2 -C 6 )alkyl, guanidino, guanidino(C 1 -C 6 )alkyl, amidino, amidino(C j —C 6 )alkyl, thiol, (C 1 -C 6 )alkylthiol, alkylthioalkyl of 2-10 carbon atoms, N-containing heterocyclyl, N-containing heterocyclyl(C 1 -C 6 )alkyl, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolylalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms, and aryl(C 1 -C 6 )alkyl; where each R moiety is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C 1 -C 6 )alkoxy, and the peptoid region -(Q) n - comprises at least 3 N-substituted glycines wherein R is a moiety that is charged at physiologically relevant pH. 
     
     
         9 . The peptoid reagent of any  claim 8  wherein the charged N-substituted glycines comprise a charged R moiety that is independently selected from amino(C 1 -C 6 )alkyl, ammonium(C 1 -C 6 )alkyl, guanidino, guanidino(C 1 -C 6 )alkyl, amidino, amidino(C 1 -C 6 )alkyl, N-containing heterocyclyl, and N-containing heterocyclyl(C 1 -C 6 )alkyl, wherein each R moiety is optionally substituted with 1-3 substituents independently selected from halogen, C 1 -C 3  methoxy, and C 1 -C 3  alkyl. 
     
     
         10 . The peptoid reagent of  claim 1 , wherein at least one amino acid of said peptide fragment is replaced by an N-substituted glycine according to the following replacement scheme:
 (a) Ala, Gly, Ile, Leu, Pro, and Val can be replaced by N-(alkyl)glycine, N-(aralkyl)glycine, or N-(heteroarylalkyl)glycine;   (b) Asp, Asn, Cys, Gln, Glu, Met, Ser, and Thr can be replaced by N-(hydroxyalkyl)glycine, N-(alkoxy)glycine, N-(aminoalkyl)glycine,   or N-(guanidinoalkyl)glycine;   (c) Phe, Trp, and Tyr can be replaced by N-(aralkyl)glycine, N-(heteroarylalkyl)glycine, N-(hydroxyaralkyl)glycine, or N-(alkoxyaralkyl)glycine; and   (d) Arg, His, and Lys can be replaced by N-(aminoalkyl)glycine or N-(guanidinoalkyl)glycine.   
     
     
         11 . The peptoid reagent of  claim 10 , wherein the peptide fragment is selected from the group consisting of SEQ ID Nos. 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 135, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, and 228. 
     
     
         12 . The peptoid reagent of  claim 10 , wherein the peptide fragment is selected from the group consisting of SEQ ID Nos. 14, 50, 51, 52, 12, 72, 68, and 115-219. 
     
     
         13 . The peptoid reagent of  claim 10 , wherein the peptide fragment is selected from the group consisting of SEQ ID Nos. 14, 50, and 68. 
     
     
         14 . The peptoid reagent of  claim 13 , wherein the peptide fragment is either SEQ ID No. 14 or 50. 
     
     
         15 . The peptoid reagent of  claim 13 , wherein the peptide fragment is SEQ ID No. 14. 
     
     
         16 . The peptoid reagent of  claim 13 , wherein the peptide fragment is SEQ ID No. 50. 
     
     
         17 . The peptoid reagent of  claim 13 , wherein the peptide fragment is SEQ ID No. 68. 
     
     
         18 . The peptoid reagent of  claim 1 , comprising at least one conjugate moiety. 
     
     
         19 . The peptoid reagent of  claim 18 , wherein the conjugate moiety is attached through a linker moiety. 
     
     
         20 . The peptoid reagent of  claim 18 , wherein the conjugate moiety is a cross-linking agent or a binding agent. 
     
     
         21 . The peptoid reagent of  claim 18 , wherein the conjugate moiety comprises biotin or a mercapto group. 
     
     
         22 . The peptoid reagent of  claim 1 , wherein the conformational disease protein is that of a prion-related disease; the pathogenic form of the conformational disease protein is PrP Sc ; and the nonpathogenic form of the conformational disease protein is PrP C . 
     
     
         23 . The peptoid reagent of  claim 1 , wherein the peptoid reagent interacts with the pathogenic form of the conformational disease protein with an affinity of at least about 10 fold greater than that for the nonpathogenic form of the conformational disease protein. 
     
     
         24 . A peptoid reagent that interacts preferentially with PrP Sc  as compared to PrP C , wherein the peptoid reagent has formula:
   X a -(Q) n -X b      wherein:   each Q is independently an N-substituted glycine having the formula:
   —(NR—CH 2 —CO)—
 
   where each R is independently selected from (C 2 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )cycloalkyl-aryl, amino(C 1 -C 6 )alkyl, ammonium(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, carboxy, carboxy(C 2 -C 6 )alkyl, carbamyl, carbamyl(C 2 -C 6 )alkyl, guanidino, guanidino(C 1 -C 6 )alkyl, amidino, amidino(C 1 -C 6 )alkyl, thiol, (C 1 -C 6 )alkylthiol, alkylthioalkyl of 2-10 carbon atoms, N-containing heterocyclyl, N-containing heterocyclyl(C 1 -C 6 )alkyl, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolylalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms, and aryl(C 1 -C 6 )alkyl; where each R moiety is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C 1 -C 6 )alkoxy; and   -(Q) n - defines a peptoid region;   X a  is H, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, (C 1 -C 6 )acyl, amino(C 1-6 )acyl, an amino acid, an amino protecting group, or a polypeptide of 2 to about 100 amino acids, wherein X a  is optionally substituted by a conjugate moiety that is optionally attached through a linker moiety;   X b  is H, (C 1 -C 6 )alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (C 1 -C 6 )alkoxy, aryloxy, aralkoxy, a carboxy protecting group, an amino acid, or a polypeptide of 2 to about 100 amino acids, wherein X b  is optionally substituted by a conjugate moiety that is optionally attached through a linker moiety; and   n is 4, 5, 6, 7, or 8;   wherein said peptoid region -(Q) n - has a net charge of at least 3+ at physiologically relevant pH; and wherein the peptoid region -(Q) n - is designed based on a peptide fragment of a prion protein.   
     
     
         25 . A complex comprising the peptoid reagent of  claim 1 , and a pathogenic prion. 
     
     
         26 . A composition comprising the peptoid reagent of  claim 1 , attached to a solid support. 
     
     
         27 . A composition comprising the peptoid reagent of  claim 1 , and a sample. 
     
     
         28 . The composition of  claim 27 , wherein the sample is a biological sample. 
     
     
         29 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said peptoid reagent to said pathogenic prion, if present, to form a complex, and detecting the formation of said complex, wherein the formation of the complex is indicative of the presence of said pathogenic prion. 
     
     
         30 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, contacting said first complex with a second peptoid reagent of the invention, optionally detectably labeled, under conditions that allow binding of said second peptoid reagent to said pathogenic prion of said first complex to form a second complex, and detecting formation of said second complex, wherein the formation of said second complex is indicative of the presence of the pathogenic prion. 
     
     
         31 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, contacting said first complex with a second peptoid reagent of the invention, optionally detectably labeled, under conditions that allow binding of said second peptoid reagent to said pathogenic prion of said first complex to form a second complex, and detecting formation of said second complex, wherein the formation of said second complex is indicative of the presence of the pathogenic prion. 
     
     
         32 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting the sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, dissociating said pathogenic prion from said first complex thereby providing dissociated pathogenic prion, contacting said dissociated pathogenic prion with a second peptoid reagent according to  claim 1 , optionally detectably labeled, under conditions that allow binding of said second peptoid reagent to said dissociated pathogenic prion to form a second complex, and detecting the formation of said second complex, wherein the formation of said second complex is indicative of the presence of the pathogenic prion. 
     
     
         33 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, contacting said first complex with a prion-binding reagent, optionally detectably labeled, under conditions that allow binding of said prion-binding reagent to said pathogenic prion of said first complex to form a second complex, and detecting formation of said second complex, wherein the formation of said second complex is indicative of the presence of the pathogenic prion. 
     
     
         34 . The method of  claim 33 , wherein said prion-binding reagent comprises an anti-prion antibody. 
     
     
         35 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, contacting said first complex with a prion-binding reagent, optionally detectably labeled, under conditions that allow binding of said prion-binding reagent to said pathogenic prion of said first complex to form a second complex, and detecting formation of said second complex, wherein the formation of the second complex is indicative of the presence of the pathogenic prion. 
     
     
         36 . The method of  claim 35 , wherein said prion-binding reagent comprises an anti-prion antibody. 
     
     
         37 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, dissociating said pathogenic prion from said first complex thereby providing dissociated pathogenic prion, contacting said dissociated pathogenic prion with a prion-binding reagent, optionally detectably labeled, under conditions that allow binding of said prion-binding reagent to said dissociated pathogenic prion to form a second complex, and detecting the formation of said second complex, wherein the formation of said second complex is indicative of the presence of said pathogenic prion. 
     
     
         38 . The method of  claim 37 , wherein said prion-binding reagent comprises an anti-prion antibody. 
     
     
         39 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, dissociating said pathogenic prion from said first complex thereby providing dissociated pathogenic prion, contacting said dissociated pathogenic prion with a prion-binding reagent under conditions that allow binding of said prion-binding reagent to said dissociated pathogenic prion to form a second complex, and detecting the formation of said second complex using a second prion-binding reagent, optionally detectably labeled, wherein the formation of said second complex is indicative of the presence of the pathogenic prion. 
     
     
         40 . The method of  claim 39 , wherein said prion-binding reagent comprises an anti-prion antibody. 
     
     
         41 . A method for detecting the presence of a pathogenic prion in a sample, comprising contacting said sample with a prion-binding reagent under conditions that allow binding of said prion-binding reagent to the pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, contacting said first complex with a peptoid reagent of the invention, optionally detectably labeled, under conditions that allow binding of said peptoid reagent to said pathogenic prion of said first complex to form a second complex, and detecting the formation of said second complex, wherein the formation of said second complex is indicative of the presence of said pathogenic prion. 
     
     
         42 . The method of  claim 41 , wherein said prion-binding reagent comprises an anti-prion antibody. 
     
     
         43 . A method for detecting the presence of a pathogenic prion in a sample, comprising combining a solid support with a detectably labeled ligand, wherein said solid support comprises a peptoid reagent according to  claim 1 , under conditions that allow binding of said detectably labeled ligand to said peptoid reagent, wherein said peptoid reagent of said solid support has a weaker binding affinity for said ligand than for said pathogenic prion, to form a first complex, combining said sample with said first complex under conditions that allow binding of said pathogenic prion, if present in the sample, to said peptoid reagent of said first complex, thereby replacing said detectably labeled ligand of said first complex and forming a second complex comprising said peptoid reagent and said pathogenic prion, and detecting the formation of said second complex, wherein the formation of said second complex is indicative of the presence of said pathogenic prion. 
     
     
         44 . A method for detecting the presence of a pathogenic prion in a sample, comprising: contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a complex, removing unbound sample from said complex, dissociating said pathogenic prion from said complex thereby providing dissociated pathogenic prion, contacting said dissociated pathogenic prion with a second solid support under conditions that allow said dissociated pathogenic prion to adhere to said second solid support; and detecting the adhered dissociated pathogenic prion using a prion-binding reagent, optionally detectably labeled, wherein binding of said prion-binding reagent indicates the presence of said pathogenic prion. 
     
     
         45 . The method of  claim 44 , wherein said dissociating is carried out by exposing said complex to high pH or low pH. 
     
     
         46 . The method of  claim 45 , further comprising the step of neutralizing said high pH or said low pH after said dissociating. 
     
     
         47 . The method of  claim 44 , wherein said dissociated pathogenic prion is denatured. 
     
     
         48 . The method of  claim 46 , wherein said prion-binding reagent comprises an anti-prion antibody. 
     
     
         49 . A method for detecting the presence of a pathogenic prion in a sample, comprising: contacting said sample with a first peptoid reagent according to  claim 1  under conditions that allow binding of said first peptoid reagent to said pathogenic prion, if present, to form a first complex, removing unbound sample from said first complex, dissociating said pathogenic prion from said first complex thereby providing dissociated pathogenic prion, contacting said dissociated pathogenic prion with a second solid support, wherein said second solid support comprises a first anti-prion antibody, under conditions that allow said dissociated pathogenic prion to bind to said first anti-prion antibody to form a second complex; and detecting said dissociated pathogenic prion of said second complex with a second anti-prion antibody, optionally detectably labeled, wherein binding of said second-anti-prion antibody indicates the presence of said pathogenic prion. 
     
     
         50 . The method of  claim 49 , wherein said dissociating is carried out by exposing said first complex to high pH or low pH. 
     
     
         51 . The method of  claim 50 , further comprising the step of neutralizing said high pH or said low pH after said dissociating. 
     
     
         52 . The method of  claim 49 , wherein said dissociated pathogenic prion is denatured. 
     
     
         53 . The method of  claim 49 , wherein said first prion-binding reagent comprises an anti-prion antibody. 
     
     
         54 . The method of  claim 49 , wherein second prion-binding reagent comprises an anti-prion antibody. 
     
     
         55 . A method of treating or preventing a prion-related disease comprising administering to an animal therapeutically effective amounts of one or more peptoid reagents according to  claim 1 . 
     
     
         56 . A method of treating or preventing a prion-related disease in an animal comprising determining the presence of one or more pathogenic prions in said animal; and
 (a) administering a therapeutically effective amount of one or more peptoid reagents of  claim 1  to said animal; or   (b) administering a therapeutically effective amount of one or more conventional medicaments to said animal.   
     
     
         57 . A method of determining a location of a prion-related disease infection in an animal comprising:
 (a) administering to said animal a peptoid reagent of  claim 1 , wherein said peptoid reagent is linked to an imaging agent; and   (b) detecting said imaging agent, wherein detection of said imaging agent determines the location of said infection.   
     
     
         58 . A method of treating or preventing prion-related disease in an animal comprising:
 (a) administering to said animal a therapeutically effective amount of a first dose comprising a peptoid reagent of  claim 1 ; and   (b) administering to the animal a second dose comprising a peptoid reagent of  claim 1  in an amount sufficient to induce an immune response in the animal.   
     
     
         59 . A method for isolating a pathogenic prion from a sample comprising:
 (a) contacting a solid support comprising a peptoid reagent of  claim 1  with said sample under conditions that allow binding of said pathogenic prion, if present in the sample, to said peptoid reagent to form a complex; and   (b) removing unbound sample from said complex, thereby providing isolated pathogenic prion.   
     
     
         60 . A method for reducing the amount of the pathogenic prion in a sample comprising:
 (a) contacting solid support comprising a peptoid reagent of  claim 1  with said sample under conditions that allow binding of said pathogenic prion, if present in said sample, to said peptoid reagent of said solid support to form a complex; and   (b) separating unbound sample from said complex, thereby providing said sample with a reduced amount of the pathogenic prion.   
     
     
         61 . The method of  claim 60 , wherein the amount of the pathogenic prion in the recovered sample is reduced below a detectable level. 
     
     
         62 . The method of  claim 60 , wherein the amount of the pathogenic prion is reduced by about 95 to 100%. 
     
     
         63 . A method of preparing a blood supply that is substantially free of a pathogenic prion comprising:
 (a) detecting the presence or absence of pathogenic prion in a plurality of blood samples, wherein said detecting involves binding of said pathogenic prion, if present, to a peptoid reagent of  claim 1 ; and   (b) combining said samples in which the pathogenic prion is not detected, thereby providing the blood supply that is substantially free of the pathogenic prion.   
     
     
         64 . A method of preparing a food supply that is substantially free of a pathogenic prion comprising:
 (a) detecting the presence or absence of pathogenic prion in a plurality of food samples, wherein said detecting involves binding of said pathogenic prion, if present, to a peptoid reagent of  claim 1 ; and   (b) combining said samples in which the pathogenic prion is not detected, thereby providing said food supply that is substantially free of the pathogenic prion.