Stabilized minimal coiled-coil mimetics

A macrostructure comprising:

• (i) an antiparallel coiled-coil structure of formula:
• 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 formula
• 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.