Click nucleic acid polymers and methods of making
AssigneeThe Regents of the University of Colorado, a body corporate
InventorsChristopher N. BOWMAN, Xun HAN, Benjamin D. FAIRBANKS
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Abstract
Disclosed herein are Click Nucleic Acid Polymers (CNA-polymers) that comprise one or more units which can anneal to complementary units in a manner which affords hybridization of the disclosed CNA's to synthetic or naturally occurring polymers. Also disclosed are nanoparticle/CNA conjugate. Further disclosed are methods for preparing the disclosed polymers and nanoparticle/polymer conjugates.
Claims42
A nanoparticle click nucleic acid polymer conjugate, having the formula:
- wherein the symbol:
- represents a nanoparticle;
- X2 has the formula:
- X3 has the formula:
- Y has the formula:
- each Z is the same or a different moiety capable of annealing to a complementary moiety;
- and
- the index m is an integer from 0 to 20.
A nanoparticle click nucleic acid polymer conjugate, having the formula:
- wherein the symbol:
- represents a nanoparticle;
- X2 has the formula:
- X3 has the formula:
- X4 has the formula:
- X4 has the formula:
- and
- Y has the formula:
- each Z is the same or a different moiety capable of annealing to a complementary moiety;
- and
- the indices m and n are integers independently from 0 to 20.
A process for preparing a monomer having the formula:
- suitable for use in preparing Click Nucleic Acid (CNA) polymers, comprising:
- A) reacting 2-chloro-N-(2-chloroethyl)-N-vinylacetamide with a nucleobase to form a compound having the formula:
- wherein NB is a nucleobase chosen from adenine, guanine, thymine, uracil or cytosine;
- B) reacting the compound formed in step (A) with potassium thioacetate under Finkelstein reaction conditions to form a compound having the formula:
- and
- C) reacting the compound formed in step (B) with a base to form a monomer having the formula:
A process for preparing a click nucleic acid polymer having the formula:
- [X1]—[X2]m—[X3];
- said process comprising:
- A) irradiating a monomer having the formula:
- with a source of radiation to form a reaction product admixture comprising:
- i) a click nucleic acid polymer having the formula:
- and
- ii) a thiomorpholine by-product having the formula:
- and
- B) adding the admixture to a solvent which precipitates the click nucleic acid polymer;
- NB is a nucleobase and the index m is an integer from 0 to 20.
A process for forming a nanoparticle click nucleic acid conjugate having the formula:
- wherein the symbol:
- represents a nanoparticle;
- X2 has the formula:
- X3 has the formula:
- Y has the formula:
- Z is a nucleobase;
- and
- m is an integer from 0 to 20;
- wherein said method comprises:
- A) reacting a nanoparticle precursor with one or more surface modifying agents to form a surface modified nanoparticle;
- B) reacting the surface modified nanoparticle with mercaptoethanol to form a mercaptoethanol-modified nanoparticle;
- and
- C) reacting the mercaptoethanol-modified nanoparticle with a CNA polymer to form a nanoparticle click nucleic acid polymer conjugate.
Dependencies are inferred from the claim text.