Protein-Templated Reactions Using DNA-Antibody Conjugates

TY - JOUR

T1 - Protein-Templated Reactions Using DNA-Antibody Conjugates

AU - Pellejero, Lorena Baranda

AU - Nijenhuis, Minke A. D.

AU - Ricci, Francesco

AU - Gothelf, Kurt

PY - 2023/3

Y1 - 2023/3

N2 - DNA-templated chemical reactions have found wide applications in drug discovery, programmed multistep synthesis, nucleic acid detection, and targeted drug delivery. The control of these reactions has, however, been limited to nucleic acid hybridization as a means to direct the proximity between reactants. In this work a system capable of translating protein-protein binding events into a DNA-templated reaction which leads to the covalent formation of a product is introduced. Protein-templated reactions by employing two DNA-antibody conjugates that are both able to recognize the same target protein and to colocalize a pair of reactant DNA strands able to undergo a click reaction are achieved. Two individual systems, each responsive to human serum albumin (HSA) and human IgG, are engineered and it is demonstrated that, while no reaction occurs in the absence of proteins, both protein-templated reactions can occur simultaneously in the same solution without any inter-system crosstalk.

AB - DNA-templated chemical reactions have found wide applications in drug discovery, programmed multistep synthesis, nucleic acid detection, and targeted drug delivery. The control of these reactions has, however, been limited to nucleic acid hybridization as a means to direct the proximity between reactants. In this work a system capable of translating protein-protein binding events into a DNA-templated reaction which leads to the covalent formation of a product is introduced. Protein-templated reactions by employing two DNA-antibody conjugates that are both able to recognize the same target protein and to colocalize a pair of reactant DNA strands able to undergo a click reaction are achieved. Two individual systems, each responsive to human serum albumin (HSA) and human IgG, are engineered and it is demonstrated that, while no reaction occurs in the absence of proteins, both protein-templated reactions can occur simultaneously in the same solution without any inter-system crosstalk.

KW - bioconjugation

KW - DNA templated reactions

KW - nanotechnology

KW - proteins

KW - proximity effect

KW - MULTISTEP ORGANIC-SYNTHESIS

KW - NANOSTRUCTURES

KW - LIGATION

KW - BINDING

KW - RNA

UR - http://www.scopus.com/inward/record.url?scp=85127226698&partnerID=8YFLogxK

U2 - 10.1002/smll.202200971

DO - 10.1002/smll.202200971

M3 - Journal article

C2 - 35344264

SN - 1613-6810

VL - 19

JO - Small

JF - Small

IS - 13

M1 - 2200971

ER -