# US 11,440,938 B2 · Stabilized minimal coiled-coil mimetics

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,440,938 B2
- Document ID: US11440938B2
- Status: Granted
- Kind: B2
- Application number: 17/003,686
- Filed: 2020-08-26
- Published: 2021-09-09
- Granted: 2022-09-13
- Earliest claimed: 2015-06-08
- Assignees: New York University
- Applicants: New York University
- Inventors: Paramjit S. Arora; Michael G. Wuo
- Web page: https://patentgrep.com/patent/US11440938B2

## CPC

- C07K 7/06: having 5 to 11 amino acids
- A61P 35/02: specific for leukemia
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C07K 2319/73: containing coiled-coiled motif (leucine zippers)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

This invention relates to a macrostructure that includes an antiparallel coiled-coil structure or a parallel coiled-coil structure.

## Claims

### Claim 1

A macrostructure comprising:
(i) an antiparallel coiled-coil structure of FIG. 14
wherein:
each ∘ and each ⊗ is independently absent or a modified or unmodified amino acid residue or analogue thereof, with the proviso that at least seven contiguous amino acid residues/analogues are present in each coil, wherein
a, b, c, d, e, f, g, a′, b′, c′, d′, e′, f′, and g′ indicate the location of the amino acid residues/analogues within the coiled-coil structure and
each ⊗ amino acid residue is a modified or unmodified amino acid selected from the group consisting of cysteine, homocysteine, selenocysteine, leucine, isoleucine, hexafluoroleucine, valine, hexafluorovaline, allylglycine, threonine, and analogues of each of the preceding residues;
each is absent or a covalent linker (Linker) between two amino acid residues/analogues, wherein:
each Linker A is independently a linker between a g* amino acid residue and a g′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the g* amino acid residue and the Cα position of the g′* amino acid residue is 10-25 Å;
each Linker B is independently a linker between an a* amino acid residue and a d′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the a* amino acid residue and the Cα position of the d′* amino acid residue is 5-15 Å;
each Linker C is independently a linker between a d* amino acid residue and an a′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the d* amino acid residue and the Cα position of the a′* amino acid residue is 5-15 Å;
each Linker D is independently a linker between an e* amino acid residue and an e′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the e* amino acid residue and the Cα position of the e′* amino acid residue is 10-25 Å;
and
at least one Linker A or Linker D is present;
each is a point of attachment from a terminal nitrogen to H, —PG1, —C(O)R, —C(O)NR2, —C(O)NH2, —R, —C(O)OR, an amino acid, a peptide, a tag, or a targeting moiety, where each R is independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, a heteroaryl, a heterocyclyl, an arylalkyl, a peptide, a targeting moiety, or a tag; and wherein PG1 is a protecting group for protection of an amine; and
each is a point of attachment from a terminal carbonyl to H, —OPG2, —NPG2, —OR, —OH, —NR2, —NH2, —NRC(O)C1-6 alkyl, —NHC(O)C1-6 alkyl, an amino acid, a peptide, a tag, or a targeting moiety, where each R is independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, a heteroaryl, a heterocyclyl, an arylalkyl, a peptide, a targeting moiety, or a tag; and wherein PG2 is a protecting group for protection of a carboxylic acid;
or (ii) a parallel coiled-coil structure of FIG. 15
wherein:
each ∘ and each ◯ is independently absent or a modified or unmodified amino acid residue or analogue thereof, with the proviso that at least seven contiguous amino acid residues/analogues are present in each coil, wherein
a, b, c, d, e, f, g, a′, b′, c′, d′, e′, f′, and g′ indicate the location of the amino acid residues/analogues within the coiled-coil structure and
each ⊗ amino acid residue is a modified or unmodified amino acid selected from the group consisting of cysteine, homocysteine, selenocysteine, leucine, isoleucine, hexafluoroleucine, valine, hexafluorovaline, allylglycine, threonine, and analogues of each of the preceding residues;
each is absent or a covalent linker (Linker) between two amino acid residues/analogues, wherein:
each Linker E is independently a linker between a g* amino acid residue and an e′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the g* amino acid residue and the Cα position of the e′* amino acid residue is 10-25 Å;
each Linker F is independently a linker between a d* amino acid residue and a d′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the d* amino acid residue and the Cα position of the d′* amino acid residue is 5-15 Å;
each Linker G is independently a linker between an a* amino acid residue and an a′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the a* amino acid residue and the Cα position of the a′* amino acid residue is 5-15 Å;
each Linker H is independently a linker between an e* amino acid residue and a g′* amino acid residue, wherein the length of the linker is such that the spatial distance between the Cα position of the e* amino acid residue and the Cα position of the g′* amino acid residue is 10-25 Å; and
at least one Linker E or Linker H is present; and
each is a point of attachment from a terminal nitrogen to H, —PG1, —C(O)R, —C(O)NR2, —C(O)NH2, —R, —C(O)OR, an amino acid, a peptide, a tag, or a targeting moiety, where each R is independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, a heteroaryl, a heterocyclyl, an arylalkyl, a peptide, a targeting moiety, or a tag; and wherein PG1 is a protecting group for protection of an amine; and
each is a point of attachment from a terminal carbonyl to H, —OPG2, —NPG2, —OR, —OH, —NR2, —NH2, —NRC(O)C1-6 alkyl, —NHC(O)C1-6 alkyl, an amino acid, a peptide, a tag, or a targeting moiety, where each R is independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, a heteroaryl, a heterocyclyl, an arylalkyl, a peptide, a targeting moiety, or a tag; and wherein PG2 is a protecting group for protection of a carboxylic acid.

### Claim 2 (depends on 1)

The macrostructure of claim 1, wherein each Linker is independently selected from the group, consisting of alkylene, alkenylene, arylene, heteroarylene, ethers, thioethers, amides, maleimides, esters, disulfides, diselenides, —O—, —S—, —Se—, and any combination thereof.

### Claim 3 (depends on 2)

The macrostructure of claim 2, wherein at least one of Linker A, Linker D, Linker E, and Linker H has the formula —Zn—, wherein n is a number from 1 to 25 and each Z is independently selected at each occurrence thereof from the group consisting of alkylene, alkenylene, arylene, heteroarylene, triazole-diyl, thiazole-diyl, oxazole-diyl, ethers, amides, esters, maleimides, thioethers, O, S, and Se.

### Claim 4 (depends on 3)

The macrostructure of claim 3, wherein the at least one of Linker A, Linker D, Linker E, and Linker H is independently selected from the group consisting of
wherein each marks a connection point to the Cα carbon in a linked residue/analogue.

### Claim 5 (depends on 3)

The macrostructure of claim 3, wherein the at least one of Linker A, Linker D, Linker E, and Linker H:
(i) has the formula
wherein:
Q1 is a C1-8 alkylene or a moiety of formula (C1-8 alkylene-X—C0-8 alkylene)n;
Q2 is C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene, a moiety of formula C1-8 alkylene-X—C1-8 alkylene, or a moiety of formula -Q4-Q5-Q6-; wherein each C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene can be optionally substituted from 1 to 4 (1, 2, 3, or 4) times with substituents independently selected at each occurrence thereof from the group consisting of H, halogen, C1-8 alkyl, ═C(O), NHR, N(R)2, OR, and SR;
Q3 is a C1-8 alkylene or a moiety of formula (C1-8 alkylene-X—C0-8 alkylene)n;
Q4 is selected from the group consisting of O, —C(O)—NR—, —NR—C(O)—, —C(O)—O—, —O—C(O)—, —C(O)—S—, —S—C(O)—, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene, wherein each C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene can be optionally substituted from 1 to 4 (1, 2, 3, or 4) times with substituents independently selected at each occurrence thereof from the group consisting of H, halogen, C1-8 alkyl, ═C(O), NHR, N(R)2, OR, and SR;
Q5 is selected from the group consisting of —C(O)—NR—, —NR—C(O)—, —C(O)—O—, —O—C(O)—, —C(O)—S—, S—C(O)—, C1-8 alkylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene, or is a moiety of formula C1-8 alkylene-(X—C1-8 alkylene)n, wherein each of C1-8 alkylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene can be optionally substituted from 1 to 4 (1, 2, 3, or 4) times with substituents independently selected at each occurrence thereof from the group consisting of H, halogen, C1-8 alkyl, ═C(O), NHR, N(R)2, OR, and SR;
Q6 is selected from the group consisting of O, —C(O)—NR—, —NR—C(O)—, —C(O)—O—, —O—C(O)—, —C(O)—S—, —S—C(O)—, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene, wherein each C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, monocyclic carbocycle, fused bicyclic carbocycle, non-aromatic heterocycle, arylene, and heteroarylene can be optionally substituted from 1 to 4 (1, 2, 3, or 4) times with substituents independently selected at each occurrence thereof from the group consisting of H, halogen, C1-8 alkyl, ═C(O), NHR, N(R)2, OR, and SR;
each X is selected from the group consisting of O, S, CR2, NR, P, C2-8 alkynylene, arylene, and heteroarylene (preferably O, S, CH2, NR, or CR≡CR);
each R is independently H, C1-8 alkyl, or aryl;
n is 1 to 10; and
each marks a connection point to the Cα carbon in a linked residue/analogue;
(ii) has the following formula
wherein X is O, S, CR2, NR, or P (preferably O, S, CH2 or NR), wherein X1 is O, S, NH, and NR, wherein each R is independently H, alkyl, or aryl, wherein Y is S, and wherein each marks a connection point to the Cα carbon in a linked residue/analogue; or
(iii) has the following formula
wherein X is O, S, CR2, NR, or P (preferably O, S, CH2 or NR), wherein X1 is O, S, C, CR, N, NH, and NR, wherein each R is independently H, alkyl, or aryl, wherein Y is S, and wherein each marks a connection point to the Cα carbon in a linked residue/analogue.

### Claim 6 (depends on 1)

The macrostructure of claim 1, wherein the at least one of Linker B, Linker C, Linker F, and Linker G is independently selected from the group consisting of disulfides, diselenides, C1-8 alkylene, C2-8 alkenylene, arylene, heteroarylene, triazole-diyl, and thiazole-diyl.

### Claim 7 (depends on 6)

The macrostructure of claim 6, wherein the at least one of Linker B, Linker C, Linker F, and Linker G is independently a disulfide bond from a cysteine or homocysteine residue, a diselenide from a selenocysteine residue, an alkylene from an allylglycine residue, or an arylene linker.

### Claim 8 (depends on 1)

The macrostructure of claim 1, wherein one Linker is present.

### Claim 9 (depends on 1)

The macrostructure of claim 1, wherein (i) at least one Linker A or Linker D is present and at least one Linker B or Linker C is present or (ii) as least one Linker E or Linker H is present and at least one Linker F or Linker G is present.

### Claim 10 (depends on 9)

The macrostructure of claim 9, wherein (i) one Linker A or Linker D is present and one Linker B or Linker C is present or (ii) one Linker E or Linker H is present and one Linker F or Linker G is present.

### Claim 11 (depends on 1)

The macrostructure of claim 1, wherein the antiparallel coiled-coil structure is an antiparallel coiled-coil of Formula III:
wherein:
a1*, a2*, a3*, b1, b2, b3, c1, c2, c3, d1*, d2*, d3*, e1*, e2*, e3*, f1, f2, f3, g0*, g1*, g2*, a1′*, a2′*, a3′*, b2′, b3′, c1′, c2′, c3′, d1′*, d2′*, d3′*, e1′*, e2′*, e3′*, f0′, f2′, g0′*, g1′*, and g2′* are each independently absent or a modified or unmodified amino acid residue or analogue thereof, with the proviso that at least seven contiguous amino acid residues/analogues are present in each coil;
a1*, a2*, a3*, d1*, d2*, d3*, a1′*, a2′*, a3′*, d1′*, d2′*, and d3′* each independently have the formula (a)
wherein:
R1a, R1b, R1c, and R1d are each independently hydrogen, an amino acid side chain, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl, wherein each amino acid side chain, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and arylalkyl can be optionally substituted with H, an alkyl, an alkenyl, an alkynyl, an azide, —OR5, or —SR5; and at least one of R1a and R1c is a side chain of a modified or unmodified amino acid selected from the group consisting of cysteine, homocysteine, selenocysteine, leucine, isoleucine, hexafluoroleucine, valine, hexafluorovaline, allylglycine, threonine, and analogues of each of the preceding residues; and
when a Linker B or a Linker C is attached to the residue of formula (a), the Linker B or Linker C is attached to or replaces one of R1a, R1b, R1c, and R1d;
e1*, e2*, e3*, g1*, g2*, e1′*, e2′*, e3′*, g0′*, g1′*, and g2′* each independently have the formula (b) and g0* has the formula (b′)
wherein:
R2a, R2b, R2c, and R2d are each independently hydrogen, an amino acid side chain, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl, wherein each amino acid side chain, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and arylalkyl can be optionally substituted with H, an alkyl, an alkenyl, an alkynyl, an azide, —OR5, or —SR5; and at least one of R2a and R2c is an amino acid side chain; and
when a Linker A or a Linker D is attached to a residue of formula (b), the Linker A or Linker D is attached to or replaces one of R2a, R2b, R2c, and R2d;
b1, b2, b3, c1, c2, c3, f1, f2, f3, b1′, b2′, b3′, c1′, c2′, c3′, f1′, and f2′ each independently have the formula (c) and f0′ has the formula (c′)
wherein each R3 is independently hydrogen, an amino acid side chain, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl, wherein each amino acid side chain, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and arylalkyl can be optionally substituted with H, an alkyl, an alkenyl, an alkynyl, an azide, —OR5, or —SR5;
each R4 is independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl; and
each R5 in Formula III is independently selected from the group consisting of H, —PG (where PG is a protecting group), an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, a heteroaryl, a heterocyclyl, and an arylalkyl.

### Claim 12 (depends on 11)

The macrostructure of claim 11, wherein at least one of the following conditions is met:
(A) in at least one residue of formula (a), (i) one of R1a and R1c is the side chain of a modified or unmodified amino acid selected from the group consisting of cysteine, homocysteine, selenocysteine, leucine, isoleucine, hexafluoroleucine, valine, hexafluorovaline, allylglycine, threonine, and analogues of each of the preceding residues, and (ii) R1b, R1d, and the other of R1a and R1c are each independently hydrogen, a C1-3 alkyl, or a C2-3 alkenyl;
(B) in at least one residue of formula (b), (i) one of R2a and R2c is an amino acid side chain and (ii) R2b, R2d, and the other of R2a and R2c are each independently hydrogen or a C1-3 alkyl.

### Claim 13 (depends on 1)

The macrostructure of claim 1, wherein the parallel coiled-coil structure is a parallel coiled-coil of Formula IV:
wherein:
a1*, a2*, a3*, b1, b2, b3, c1, c2, c3, d1*, d2*, d3*, e1*, e2*, e3*, f0, f1, f2, g0*, g1*, g2*, a1′*, a2′*, a3′*, b1′, b2′, b3′, c1′, c2′, c3′, d1′*, d2′*, d3′*, e1′*, e2′*, e3′*, f0′, f1′, f2′, g0′*, g1′*, and g2′* are each independently absent or a modified or unmodified amino acid residue or analogue thereof, with the proviso that at least seven contiguous amino acid residues/analogues are present in each coil;
a1*, a2*, a3*, d1*, d2*, d3*, a1′*, a2′*, a3′*, d1′*, d2′*, and d3′* each independently have the formula (a)
wherein:
R1a, R1b, R1c, and R1d are each independently hydrogen, an amino acid side chain, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl, wherein each amino acid side chain, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and arylalkyl can be optionally substituted with H, an alkyl, an alkenyl, an allkynyl, an azide, —OR5, or —SR5; and at least one of R1a and R1c is a side chain of a modified or unmodified amino acid selected from the group consisting of cysteine, homocysteine, selenocysteine, leucine, isoleucine, hexafluoroleucine, valine, hexafluorovaline, allylglycine, threonine, and analogues of each of the preceding residues; and
when a Linker B or a Linker C is attached to the residue of formula (a), the Linker B or Linker C is attached to or replaces one of R1a, R1b, R1c, and R1d;
e1*, e2*, e3*, g0*, g1*, g2*, e1′*, e2′*, e3′*, g0′*, g1′*, and g2′* each independently have the formula (b)
wherein:
R2a, R2b, R2c, and R2d are each independently hydrogen, an amino acid side chain, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl, wherein each amino acid side chain, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and arylalkyl can be optionally substituted with H, an alkyl, an alkenyl, an alkynyl, an azide, —OR5, or —SR5; and at least one of R2a and R2c is an amino acid side chain; and
when a Linker A or a Linker D is attached to a residue of formula (b), the Linker A or Linker D is attached to or replaces one of R2a, R2b, R2c, and R2d;
b1, b2, b3, c1, c2, c3, f1, f2, b1′, b2′, b3′, c1′, c2′, c3′, f1′, and f2′ each independently have the formula (c) and f0 and f0′ have the formula (c′)
wherein each R3 is independently hydrogen, an amino acid side chain, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl, wherein each amino acid side chain, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, and arylalkyl can be optionally substituted with H, an alkyl, an alkenyl, an alkynyl, an azide, —OR5, or —SR5;
each R4 is independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a heterocyclyl, an aryl, a heteroaryl, or an arylalkyl; and
each R5 is independently selected from the group consisting of H, —PG (where PG is a protecting group), an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, a heteroaryl, a heterocyclyl, and an arylalkyl.

### Claim 14 (depends on 13)

The macrostructure of claim 13, wherein at least one of the following conditions is met:
(A) in at least one residue of formula (a), (i) one of R1a and R1c is the side chain of a modified or unmodified amino acid selected from the group consisting of cysteine, homocysteine, selenocysteine, leucine, isoleucine, hexafluoroleucine, valine, hexafluorovaline, allylglycine, threonine, and analogues of each of the preceding residues, and (ii) R1b, R1d, and the other of R1a and R1c are each independently hydrogen, a C1-3 alkyl, or a C2-3 alkenyl;
(B) in at least one residue of formula (b), (i) one of R2a and R2c is an amino acid side chain and (ii) R2b, R2d, and the other of R2a and R2c are each independently hydrogen or a C1-3 alkyl.

### Claim 15 (depends on 1)

The macrostructure of claim 1, wherein:
(i) the first strand of the antiparallel coiled-coil structure comprises at least ten contiguous modified or unmodified amino acid residues (or analogues thereof), wherein the at least ten contiguous amino acid residues/analogues have the formula gX1-X2-X3-X4-X5-X6-X7-X8-X9-X10b, wherein X1 is Glu, Leu, Arg, Lys, Thr, or Val (or analogues of each of the preceding residues); X2 is Cys, HCys, Leu, Ile, allylleucine, Val, allylglycine, Thr, selenocysteine, hexafluoroleucine, or hexafluorovaline (or analogues of each of the preceding residues); X3 is any residue/analogue; X4 is His, Tyr, Phe, Lys, Gln, or Trp (or analogues of each of the preceding residues); X5 is Cys, HCys, Leu, le, allylleucine, Val, allylglycine, Thr, selenocysteine, hexafluoroleucine, or hexafluorovaline (or analogues of each of the preceding residues); X6 is any residue/analogue; X7 is Glu, Asn, Trp, Leu, Glu, or Gln (or analogues of each of the preceding residues); X8 is Leu, Met, Ala, His, or Ser (or analogues of each of the preceding residues); X9 is Cys, HCys, Leu, Ile, allylleucine, Val, allylglycine, Thr, selenocysteine, hexafluoroleucine, or hexafluorovaline (or analogues of each of the preceding residues); and X10 is any residue/analogue;
(ii) the second strand of the antiparallel coiled-coil structure comprises at least ten contiguous modified or unmodified amino acid residues (or analogues thereof), wherein the at least ten contiguous amino acid residues/analogues have the formula c′X1′-X2′-X3′-X4′-X5′-X6′-X7′-X8′-X9′-X10e′, wherein X1′ is Glu, Asn, Leu, Gln, Met, or Ala (or analogues of each of the preceding residues); X2′ is Cys, HCys, Leu, Ile, allylleucine, Val, allylglycine, Thr, selenocysteine, hexafluoroleucine, or hexafluorovaline (or analogues of each of the preceding residues); X3′ is any residue/analogue; X4′ is any residue/analogue; X5′ is Ala, Ser, Thr, Gly, or Asp (or analogues of each of the preceding residues); X6′ is Cys, HCys, Leu, Ile, allylleucine, Val, allylglycine, Thr, selenocysteine, hexafluoroleucine, or hexafluorovaline (or analogues of each of the preceding residues); X7′ is Arg, Leu, Gln, Met, Glu, or Asp (or analogues of each of the preceding residues); X8′ is Tyr, Val, Phe, Trp, or Met (or analogues of each of the preceding residues); X9′ is Cys, HCys, Leu, Ile, allylleucine, Val, allylglycine, Thr, selenocysteine, hexafluoroleucine, or hexafluorovaline (or analogues of each of the preceding residues); and X10′ is any residue/analogue;
(iii) g, b, c′, and e′ indicate where the ten contiguous amino acids/analogues appear within the antiparallel coiled-coil structure;
(iv) residues in the e/e′ and g/g′ positions can be optionally modified to facilitate attachment of a Linker or replaced with a Linker, if present; and
(v) residues in the a/a′ and d/d′ positions can be optionally modified to facilitate attachment of a Linker, if present.

### Claim 16 (depends on 15)

The macrostructure of claim 15, wherein:
(i) X1 is Glu (or analogue thereof); X2 is Leu (or analogue thereof); X3 is Trp (or analogue thereof); X4 is His (or analogue thereof); X5 is Leu (or analogue thereof); X6 is any residue/analogue; X7 is Glu (or analogue thereof); X8 is Leu (or analogue thereof); X9 is Leu (or analogue thereof); and X10 is Trp (or analogue thereof);
(ii) X1′ is Glu (or analogue thereof); X2′ is Leu (or analogue thereof); X3′ is Trp (or analogue thereof); X4′ is Arg (or analogue thereof); X5′ is Ser (or analogue thereof); X6′ is Ile (or analogue thereof); X7′ is Arg (or analogue thereof); X8′ is Val (or analogue thereof); X9′ is Leu (or analogue thereof); and X10′ is any residue/analogue.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising a macrostructure according to claim 1 and a pharmaceutically acceptable vehicle.

### Claim 18 (depends on 15)

A method of inhibiting interaction between the AML1-ETO-containing transcription factor complex and an NHR2 binding motif, said method comprising:
contacting the transcription factor complex and/or the NHR2 binding motif with a macrostructure according to claim 15 under conditions effective to inhibit interaction between the AML1-ETO-containing transcription factor complex and the NHR2 binding motif.

### Claim 19 (depends on 1)

A method of modulating transcription of a gene in a cell, wherein transcription of the gene is regulated by interaction between AML1-ETO-containing transcription factor complex and an NHR2 binding motif, said method comprising:
contacting the cell with a macrostructure according to claim 1 under conditions effective to modulate transcription of the gene.

### Claim 20 (depends on 1)

A method of treating leukemia in a subject, said method comprising:
administering to the subject a macrostructure according to claim 1 under conditions effective to treat leukemia in the subject.