Compositions, assays, and methods for direct modulation of fatty acid metabolism

A method for identifying a compound that modulates myeloid cell leukemia-1 (MCL-1)/very long chain acyl CoA dehydrogenase (VLCAD) interaction, the method comprising:

• contacting an MCL-1 polypeptide and a VLCAD polypeptide with a test compound;
• and
• detecting a reduction in interaction between the MCL-1 polypeptide and the VLCAD polypeptide relative to the interaction between the MCL-1 polypeptide and the VLCAD polypeptide in the absence of the test compound, wherein detection of a reduced interaction between the MCL-1 polypeptide and the VLCAD polypeptide identifies the test compound as a compound that modulates the MCL-1/VLCAD interaction.

-55. (canceled)

-64. (canceled)

A photoreactive SAHB (pSAHB) comprising (a) an amino acid sequence set forth in any one of SEQ ID NOs.43-60, except for 1 to 5 amino acid substitutions, wherein the pSAHB binds to VLCAD and/or MCL-1;

• (b) an amino acid sequence set forth in any one of SEQ ID NOs:61-63, or (c) an amino acid sequence set forth in any one of SEQ ID NOs:
• 11, 15, 19, 26, 28, and 30.

(canceled)

An MCL-1 SAHB peptide comprising an amino acid sequence that is identical to an amino acid sequence set forth in any one of SEQ ID NOs:

• 43-60, except for 1 to 6 amino acid substitutions, wherein the MCL-1 SAHB peptide binds to VLCAD and/or MCL-1 to disrupt VLCAD activity, wherein the MCL-1 SAHB peptide has the at least two modified amino acids “X”, and wherein each “X” in the sequence is S5.