Bioactivation of particles

Abstract

Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

1 .- 20 . (canceled) 
     
     
         21 . A bioactivation peptide for use in treating particle quantum dots having a surface to form bioactivated particles, said bioactivation peptide comprising:
 a molecular recognition part that is bindable to said surface of said quantum dot and one or more functional parts, said molecular recognition part including an amino-end and a carboxy-end and comprising one or more hydrophobic spacers and one or more binding clusters and wherein said functional part(s) is attached to said molecular recognition part at said amino-end and/or said carboxy-end,   wherein said binding cluster is directly bindable to said surface of said quantum dot and comprises an amino acid independently selected from the group consisting of cysteine, methionine, and histidine,
 wherein said hydrophobic spacer comprises an amino acid modified to be hydrophobic independently selected from the group consisting of hydrophobic alanine, hydrophobic glycine, hydrophobic isoleucine, hydrophobic leucine, hydrophobic methionine, hydrophobic arginine, hydrophobic valine, and hydrophobic tryptophan. 
   
     
     
         22 . (canceled) 
     
     
         23 . A bioactivation peptide according to  claim 21  wherein said binding cluster consists essentially of two cysteines. 
     
     
         24 . (canceled) 
     
     
         25 . A bioactivation peptide according to  claim 21  wherein said hydrophobic amino acid is hydrophobic alanine. 
     
     
         26 . (canceled) 
     
     
         27 . A bioactivation peptide according to  claim 23  wherein said hydrophobic spacer is hydrophobic alanine. 
     
     
         28 . A bioactivation peptide according to  claim 21  wherein said molecular recognition part comprises at least three binding clusters which are alternately located between at least four hydrophobic spacers. 
     
     
         29 . A bioactivation peptide according to  claim 28  wherein said binding clusters each consists essentially of two cysteines and said hydrophobic spacers each consists essentially of hydrophobic alanine. 
     
     
         30 . A bioactivation peptide according to  claim 21  wherein said quantum dot to which said molecular recognition part is bindable comprises inorganic material at said surface. 
     
     
         31 . A bioactivation peptide according to  claim 30  wherein the diameter of said particle is between 0.1 and 100 nanometers. 
     
     
         32 . (canceled) 
     
     
         33 . A bioactivation peptide according to  claim 21  wherein said functional part(s) comprises one or more functional agent(s) selected from the group consisting of solubility agents, conjugation agents, targeting agents, therapeutic agents, imaging agents, detection agents, recognition agents and diagnostic agents. 
     
     
         34 . A bioactivation peptide according to  claim 21  wherein said functional part(s) consist essentially of one or more solubility agent(s). 
     
     
         35 . A bioactivation peptide according to  claim 21  wherein said functional part(s) comprise one or more solubility agents attached to said molecular recognition part and one or more functional agent(s) attached to said one or more solubility agent(s) wherein said functional agent(s) is selected from the group consisting of conjugation agents, targeting agents, therapeutic agents, imaging agents, detection agents, recognition agents and diagnostic agents. 
     
     
         36 . A bioactivation peptide according to  claim 34  wherein said solubility agent is selected from the group consisting of hydrophilic peptides, polyethylene glycol, poly(ethylene oxide), polyelectrolytes and sugars. 
     
     
         37 .- 41 . (canceled) 
     
     
         42 . A method for making a bioactivated particle that is soluble in an aqueous medium, said method comprising the steps of:
 providing a quantum dot that includes a surface; and   treating the surface of said quantum dot with a sufficient amount of a bioactivation peptide according to  claim 21  to make said bioactivated particle soluble in said aqueous medium.   
     
     
         43 . (canceled) 
     
     
         44 . A method for making a bioactivated particle that is soluble in an aqueous medium, said method comprising the steps of:
 providing a quantum dot that includes a surface; and   treating the surface of said quantum dot with a sufficient amount of a bioactivation peptide according to  claim 34  to make said bioactivated particle soluble in said aqueous medium.   
     
     
         45 . A method for making a bioactivated particle that is soluble in an aqueous medium, said method comprising the steps of:
 providing a quantum dot that includes a surface; and   treating the surface of said quantum dot with a sufficient amount of a bioactivation peptide according to  claim 35  to make said bioactivated particle soluble in said aqueous medium.   
     
     
         46 . A bioactivated particle having the formula 
       
         
           
           
               
               
           
         
         wherein [QD] is a quantum dot, 
         wherein [BC] is a binding cluster comprising an amino acid independently selected from the group consisting of cysteine, methionine, histidine, and combinations, 
         wherein [HS] is a hydrophobic spacer comprising an amino acid modified to be hydrophobic independently selected from the group consisting of hydrophobic alanine, hydrophobic glycine, hydrophobic isoleucine, hydrophobic leucine, hydrophobic methionine, hydrophobic arginine, hydrophobic valine, and hydrophobic tryptophan, 
         wherein m is at least 1, 
         wherein [FP 1 ] and [FP 2 ] may be the same or different and are functional parts selected from the group consisting of a solubility agent, conjugation agent, targeting agent, therapeutic agent, imaging agent, detection agent, recognition agent, and diagnostic agent. 
       
     
     
         47 . The bioactivated particle of  claim 46 ,
 wherein [BC] is a binding cluster consisting of at least one cysteine,   wherein [HS] is a hydrophobic spacer consisting of at least one hydrophobic alanine,   wherein m is at most 3, and   wherein [FP 1 ] and [FP 2 ] may be the same or different and are functional parts selected from the group consisting of a hydrophilic peptide, polyethylene glycol, poly(ethylene oxide), a polyelectrolyte, polyethylene imine, a sugar, cellobiose, sucrose, sialic acid, and combinations.   
     
     
         48 . A bioactivation peptide having the formula:
   [FP 1 ]-[MRP], [MRP]-[FP 2 ], or [FP 1 ]-[MRP]-[FP 2 ],   wherein [FP 1 ] and [FP 2 ] may be the same or different and are functional parts selected from the group consisting of amide, acetyl, carboxamide, carboxyl, polyethylene glycol (PEG), NHS ester, keto, thiol, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), Ni-NTA, I, Yt, tritium, a metallo texaphyrin, taxol, herceptin, fluorescein, bromothymol blue, a hydrophilic peptide, biotin, avidin, streptavidin, lysine, cysteine, aspartic acid, DNA, transferrin, an antibody, a single chain fragment, G-S-E-S-G-G-S-E-S-G [SEQ. ID. NO. 6], G-S—S—S-G-G-S—S—S-G [SEQ. ID. NO. 7], G-P—K—K—K—R—K—V-G-G-S-E-S-G-G-S-E-S-G [SEQ. ID. NO. 8], K-G-S-E-S-G-G-S-E-S-G [SEQ. ID. NO. 9], and combinations,   wherein [MRP] is a molecular recognition part consisting of Ala-C—C-Ala-C—C-Ala-C—C-Ala [SEQ. ID. NO. 1], and   wherein Ala is hydrophobic alanine, C is cysteine, G is glycine, S is serine, E is glutamic acid, P is proline, K is lysine, R is arginine, and V is valine.   
     
     
         49 . The bioactivation peptide of  claim 48 , having the formula
   [MRP]-[FP 2 ]   wherein [FP 2 ] is selected from the group consisting of PEG, PEG-biotin, hydrophilic peptide-transferrin, and hydrophilic peptide-tyrosine-DOTA-iodine.   
     
     
         50 . The bioactivation peptide of  claim 48 , selected from the group consisting of NH 2 -Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 1], acetylated-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 1], NH 2 -G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 2], acetylated-G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 10], acetylated-G-S—S—S-G-G-S—S—S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 3], acetylated-G-P—K—K—K—R—K—V-G-G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 4], acetylated-K-G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 5], and biotin-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 1]. 
     
     
         51 . The bioactivation peptide according to  claim 21 , selected from the group consisting of NH 2 -Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 1], acetylated-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 1], NH 2 -G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 2], acetylated-G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 10], acetylated-G-S—S—S-G-G-S—S—S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 3], acetylated-G-P—K—K—K—R—K—V-G-G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 4], acetylated-K-G-S-E-S-G-G-S-E-S-G-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 5], and biotin-Ala-C—C-Ala-C—C-Ala-C—C-Ala-carboxamide [SEQ. ID. NO. 1],
 wherein Ala is hydrophobic alanine, C is cysteine, G is glycine, S is serine, E is glutamic acid, P is proline, K is lysine, R is arginine, and V is valine.