Nucleic acid-based linkers for detecting and measuring interactions

Abstract

The invention provides compositions comprising nucleic acid complexes for use in monitoring binding interactions and in measuring association and/or dissociation kinetics with or without force, detecting analytes, screening aptamers, and encoding/encrypting information. In some instances, the nucleic acid complexes are double- stranded nicked nucleic acids comprising a scaffold nucleic acid hybridized to one or more oligonucleotides. In some instances, a first and/or a second oligonucleotide are linked to moieties that are known to interact with each other or which are suspected of interacting with each other.

1 - 123 . (canceled) 
     
     
         124 . A nucleic acid complex comprising
 a single-stranded scaffold nucleic acid hybridized to a plurality of single-stranded oligonucleotides, each of which hybridizes to a contiguous nucleotide sequence, and   a bridge oligonucleotide hybridized to two non-contiguous nucleotide sequences of the scaffold nucleic acid.   
     
     
         125 . The nucleic acid complex of  claim 124 , wherein the complex comprises two or more bridge oligonucleotides, each hybridized to two non-contiguous nucleotide sequences of the scaffold nucleic acid, wherein each bridge oligonucleotide binds to different regions of the scaffold nucleic acid. 
     
     
         126 . A kit comprising
 a single-stranded scaffold nucleic acid, and   a plurality of single-stranded oligonucleotides, each having a sequence complementary to a contiguous sequence on the scaffold nucleic acid,   wherein when the oligonucleotides are hybridized to the scaffold nucleic acid no overlap exists between the oligonucleotides.   
     
     
         127 . The kit of  claim 126 , further comprising a first single-stranded oligonucleotide linked to a first binding partner. 
     
     
         128 . The kit of  claim 126 , further comprising a second single-stranded oligonucleotide linked to a second binding partner. 
     
     
         129 . The kit of  claim 126 , further comprising a third single-stranded oligonucleotide linked to a third binding partner. 
     
     
         130 . The kit of  claim 126 , further comprising a fourth single-stranded oligonucleotide linked to a fourth binding partner. 
     
     
         131 . The kit of  claim 130 , wherein the first, second, third, or fourth single-stranded oligonucleotides, or a combination thereof, are housed separately from the plurality of single-stranded oligonucleotides. 
     
     
         132 . The kit of  claim 126 , further comprising a solid support. 
     
     
         133 . The kit of  claim 132 , wherein the solid support is a bead. 
     
     
         134 . The kit of  claim 126 , wherein the first and second binding partners have binding affinity to each other, and optionally the third and fourth binding partners have binding affinity to each other. 
     
     
         135 . The kit of  claim 126 , wherein the first and second binding partners have binding affinity to an analyte that is not a binding partner bound to the single-stranded oligonucleotides of the nucleic acid complex. 
     
     
         136 . A method comprising
 detecting a rate of association or dissociation between a first and a second binding partner wherein the first and the second binding partners are linked to a nucleic acid complex comprising a single-stranded scaffold nucleic acid hybridized to a plurality of single-stranded oligonucleotides, wherein a first single-stranded oligonucleotide in the plurality is linked to the first binding partner and a second single-stranded oligonucleotide in the plurality is linked to the second binding partner,   wherein association or dissociation is detected by a change in length of the nucleic acid complex.   
     
     
         137 . A method comprising
 combining an isolated single-stranded scaffold nucleic acid with a plurality of single-stranded oligonucleotides, each having a sequence complementary to a sequence on the scaffold nucleic acid, under conditions that allow the single-stranded oligonucleotides to hybridize to the scaffold nucleic acid in a sequence-specific manner without overlap, to form a nucleic acid complex,   wherein the plurality comprises a first single-stranded oligonucleotide linked to a first binding partner.