NEMO coiled coil mimics and methods of using same

A macrostructure comprising a parallel coiled-coil, wherein the parallel coiled-coil comprises:

• a first coil of Formula I and a second coil of Formula II:
• T1-f0-g0-a1-b1-c1-d1-e1-f1-g1-a2-b2-c2-d2-e2-f2-g2-a3-b3-c3-d3-e3-T2 (Formula I) (SEQ ID NO:
• 1)
• T3-g′0-a′1-b′1-c′1-d′1-e′1-f′1-g′1-a′2-b′2-c′2-d′2-e′2-f′2-g′2-a′3-b′3-c′3-d′3-e′3-f′3-T4 (Formula II) (SEQ ID NO:
• 2),
• wherein:
• each a1-3, b1-3, c1-3, d1-3, e1-3, f0-2, g0-2, a′1-3, b′1-3, c′1-3, d′1-3, e′1-3, f′1-3, and g′0-2 is independently absent or a residue selected from the group consisting of modified or unmodified amino acid residues and analogues thereof,
• one or more of the following residue pairs are covalently bound by a linker:
• g0-e′1, g1-e′2, g2-e′3, d1-d′1, d2-d′2, d3-d′3, a1-a′1, a2a′2, a3-a3, e1-g′0, e2-g′1, and e3-g′2;
• each T1 and T3 is independently a point of attachment from a terminal nitrogen to one or more moieties, wherein each moiety is independently H, -PG1, —C(O)R, —C(O)NR2, —C(O)NH2, —R, —C(O)OR, an amino acid or analogue thereof, a peptide, a targeting moiety, or a tag, where PG1 is an amine protecting group and 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
• each T2 and T4 is independently a point of attachment from a terminal carbonyl to H, —OPG2, —NPG2, —OR, —OH, —NR2, —NH2, —N(R)C(O)C1-6 alkyl, —N(H)C(O)C1-6 alkyl, an amino acid or analogue thereof, a peptide, a targeting moiety, or a tag, where PG2 is a carboxylic acid protecting group and 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:
• the first coil comprises fourteen contiguous residues which correlate to positions f0-e2 of Formula I, wherein said fourteen contiguous residues of the first coil have the amino acid sequence of SEQ ID NO:
• 4;
• and the second coil comprises fourteen contiguous residues which correlate to positions g′0-f′2 of Formula II, wherein said fourteen contiguous residues of the second coil have the amino acid sequence of SEQ ID NO:
• 6.