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

Patent metadata

Field	Value
Publication number	US-2019025315-A1
Application number	US-201816041676-A
Country	US
Kind code	A1
Filing date	Jul 20, 2018
Priority date	Jul 21, 2017
Publication date	Jan 24, 2019
Grant date	—

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 an aryl ring or a heteroaryl ring;
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 a 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 a 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 Q independently is linker-Z or Z;
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,
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 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, a Spiegelmer, a somamer, a TNA aptamer, a XNA aptamer, a 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 solubilizing group comprises an anionic group comprising a carboxyl, an organophosphorus group, an organosulfur group, hydroxyl, thiol, or combinations thereof; 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 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 comprises an amino group and a carboxyl group; 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 an aryl ring or a heteroaryl ring;
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 another;
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 a 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 a 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,
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 and that the nanohoop compound is not

9 . The nanohoop compound of claim 8 having a structure satisfying Formula IIP

wherein n is an integer ranging from 2 to 9.

10 . The nanohoop compound of claim 8 , selected from:

11 . A method of making a nanohoop conjugate, comprising covalently coupling a biological moiety to a nanohoop compound having structure satisfying Formula I through one or more functional groups of the nanohoop compound

wherein
each of rings A, A′, B and B′ independently is an aryl ring or a heteroaryl ring;
m is an integer selected from 1 to 10;
each R independently is linker-Z or Z, wherein
the link

Assignees

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

Inventors

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

Classifications

• G01N33/533

  with fluorescent label · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• G01N33/582 Primary

  with fluorescent label · CPC title

• C12Q1/6837

  using probe arrays or probe chips (C12Q1/6874 takes precedence) · CPC title

• C07C63/331

  with all carboxyl groups bound to non-condensed rings · CPC title