Nanohoop compounds for use in biotechnology and methods of making and using the same

Patent metadata

Field	Value
Publication number	US-11555820-B2
Application number	US-201816041676-A
Country	US
Kind code	B2
Filing date	Jul 20, 2018
Priority date	Jul 21, 2017
Publication date	Jan 17, 2023
Grant date	Jan 17, 2023

Abstract

Disclosed herein are embodiments of nanohoop compounds and conjugates thereof that can be used myriad biological applications. The nanohoop compounds described herein can exhibit beneficial properties that are useful in biotechnology, such as a fluorescent tag, probe, or label.

First claim

We claim:

1. A nanohoop compound having a structure satisfying a formula

wherein
each of rings A, A′, B and B′ independently is a phenyl ring or a heteroaryl ring selected from pyridinyl, benzo[1,2-b:4,5-b′]dithiophenyl, benzo[1,2-b:4,5-b′]difuranyl, 4,4-dimethyl-4H-cyclopenta[2,1-b:3,4-b′]dithiophene, 1,5-dihydropyrrolo[2,3-f]indolyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, or 2H-benzo[d][1,2,3]triazolyl;
m is an integer selected from 1 to 10;
each R independently is linker-Z or Z, wherein the linker comprises an aliphatic group, a heteroaliphatic group, or any combination thereof; and
Z comprises an anionic solubilizing group, a peptide, an oligonucleotide, a nucleoside, a nucleotide, a protein, an aptamer, a drug, a cell, an antibody, an amino acid, a lipid, a carbohydrate, a liposome, a cyclodextrin, a porphyrin, a quenching moiety, or, (i) a functional group that facilitates coupling of the nanohoop compound with an anionic solubilizing group, a peptide, an oligonucleotide, a nucleoside, a nucleotide, a protein, an aptamer, a drug, a quenching moiety, a cell, an antibody, an amino acid, a lipid, a carbohydrate, a liposome, a cyclodextrin, or a porphyrin when R is linker-Z, or (ii) a functional group selected from

amine, aminooxy, triazole, azide, an NHS ester, or combinations thereof, when R is Z;
each Q independently is linker-Z or Z, wherein
the linker comprises an aliphatic group, a heteroaliphatic group, or any combination thereof; and
Z comprises an anionic solubilizing group, a peptide, an oligonucleotide, a nucleoside, a nucleotide, a protein, an aptamer, a drug, a cell, an antibody, an amino acid, a lipid, a carbohydrate, a liposome, a cyclodextrin, a porphyrin, an electron-donating group, an electron withdrawing group, a quenching moiety, or a functional group that facilitates coupling of the nanohoop compound with an anionic solubilizing group, a peptide, an oligonucleotide, a nucleoside, a nucleotide, a protein, an aptamer, a drug, a quenching moiety, a cell, an antibody, an amino acid, a lipid, a carbohydrate, a liposome, a cyclodextrin, or a porphyrin;

each of r′, r and n independently is an integer selected from 0 to 24;
each of s and t, when present, independently is an integer selected from 0 to 10; and
p is an integer selected from 1 to 12;
wherein R and Q are the same or different; and
provided that when each of r, r′, and n is 0, then p is at least 5; and
provided that when p is 1, then at least one of r, r′, or n is 4 or r, r′, or n independently are integers that when taken together add up to 4.

2. The nanohoop compound of claim 1 , wherein the compound has a structure satisfying any one or more of the following formulas:

wherein
each of a, b, c, and d, independently is selected from C or N;
at least one of R or Q independently comprises an anionic group;
m is an integer selected from 1 to 4;
m′ is an integer selected from 0 to 10;
each of n, r and r′ independently is an integer selected from 0 to 5;
each of s and t, when present, independently is an integer selected from 0 to 4; and
p is an integer selected from 1 to 5.

3. The nanohoop compound of claim 1 , wherein:
(i) the drug is selected from aspartame, captopril, enalapril, octreotide, desmopressin, or combinations thereof;
(ii) the peptide is a cell-penetrating peptide, an oligopeptide, a peptidic drug, an antibody, a protein, or combinations thereof;
(iii) the functional group that facilitates coupling of the nanohoop compound with the anionic solubilizing group, the peptide, the oligonucleotide, the nucleoside, the nucleotide, the protein, the aptamer, the drug, the quenching moiety, the cell, the antibody, the amino acid, the lipid, the carbohydrate, the liposome, the cyclodextrin, or the porphyrin comprises an amine, a carboxylic acid, a hydroxyl, an alkyne, an azide, a thiol, an aldehyde, an aminooxy, a triazole, or combinations thereof;
(iv) the nucleotide or nucleoside comprises an aptamer; an L-form oligonucleotide; a slow off-rate modified aptamer; a threose nucleic acid (TNA) aptamer; a xeno-nucleic acid (XNA) aptamer; a locked nucleic acid (LNA) aptamer; a catalytic aptamer; a phosphorodithioate; an inverted nucleic acid; a 2′-fluoro-, 2′-methoxy-, or 2′-amino-modified nucleotide or nucleoside; a nucleotide or nucleotide with a modified base; a primer; an oligonucleoside or oligonucleotide; or combinations thereof;
(v) the anionic solubilizing group is selected from a carboxylate, a phosphonate, a sulfonate, or a deprotonated hydroxyl group or thiol group; and/or
(vi) the amino acid comprises a proteinogenic amino acid, an unnatural amino acid, a non-proteinogenic amino acid, a homo amino acid, an N-methyl amino acid, an alpha-methyl amino acid, a beta amino acid, a delta amino acid, a gamma amino acid, a D-amino acid, an L-amino acid, a thio amino acid, a seleno amino acid, an amino sulfonic acid, or combinations thereof.

4. The nanohoop compound of claim 1 , wherein
R is linker-Z, wherein
the linker is C 1-6 aliphatic or -(L a -X-L b ) v -, wherein each of L a and L b independently is C 1-6 aliphatic; X is O or S; and v is an integer selected from 1 to 5; and
Z is a functional group that facilitates coupling of the nanohoop and comprises a triazine, —OH, an azide, a carboxyl group, SO 3 H or a salt thereof;

each of n, r, and r′ is 1;
each of s and t is 0; and
p is 2.

5. The nanohoop compound of claim 1 , wherein
each of the rings A, A′, B and B′ is phenyl;
m, n, and t are each 1;
R is Z, wherein Z comprises an amino group;
Q comprises a carboxyl group;
r and r′ are each independently 1, 2, 3, 4, or 5;
s is 0; and
p is 1, 2 or 3.

6. The nanohoop compound of claim 1 , wherein
each of the rings A, A′, B, and B′ is phenyl;
m is 1;
each of n, r, and r′ independently is 1, 2, 3, or 4;
R is Z, wherein Z is

each of s and t is 0; and
p is 1, 2, or 3.

7. The nanohoop compound of claim 1 , wherein the compound is selected from:

8. A nanohoop compound having a structure satisfying Formula I

wherein
each of rings A, A′, B and B′ independently is a phenyl ring or a heteroaryl ring selected from pyridinyl, benzo[1,2-b:4,5-b′]dithiophenyl, benzo[1,2-b:4,5-b′]difuranyl, 4,4-dimethyl-4H-cyclopenta[2,1-b:3,4-b′]dithiophene, 1,5-dihydropyrrolo[2,3-f]indolyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, or 2H-benzo[d][1,2,3]triazolyl;
m is zero and at least one ring A is attached to two other rings of the nanohoop compound by bonds that are meta-substituted relative to one

Assignees

• Univ Oregon

Inventors

• Jasti Ramesh
• Branchaud Bruce P
• White Brittany
• Lovell Terri
• Colwell Curtis

Classifications

• B82Y30/00

  Nanotechnology for materials or surface science, e.g. nanocomposites · CPC title

• G01N33/533

  with fluorescent label · CPC title

• C07H15/26

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• C07C13/28

  Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title