Native MS of coiled coils is challenging given that their assembly is driven through hydrophobicity, which is weakened when samples are transferred to the gas-phase in MS, although assembled coiled coils can be observed under certain ionization conditions. For this study, samples were analyzed at a 5:5 µM peptide/MCL-1 ratio, and hetero-dimeric peptides at a 5:5:5 µM CC-Di-A:CC-Di-B_S:MCL-1 (Fig. ). Native MS analysis for CC-Di_S/MCL-1 indicated a mixture of unbound peptide, unbound protein and peptide/protein complexes, with relatively larger amounts of free peptide and protein than complex (Fig. ). For CC-Di_S/MCL-1, both the 1:1 and 2:2 complexes were observed, with slightly more 2:2 complex present (Fig ). For CC-Di_E1 and CC-Di_E2, the 2:2 peptide/protein complexes were the predominant species. No free protein, no 1:1 peptide/protein complex, and, only trace amounts of free peptide were observed (Fig. ). These data correlate with the more potent inhibitory activities. Analysis of hetero-dimer CC-Di-A:CC-Di-B_S with MCL-1 revealed a relatively large amount of unbound peptide and protein (Fig. ), together with coiled coil/MCL-1/complexes of varied stoichiometry and composition, which, is consistent with the weaker binding potency. Analysis of CC-Tri_E1 was attempted but was not successful because of the tendency of the peptide to precipitate. In the CC-Tet_E1/MCL-1 sample large amounts of free MCL-1 were detected alongside free monomeric peptide; 1:1 and 2:2 complexes were the only peptide/protein complexes detected and no tetrameric peptide scaffold alone or associated with 1 to 4 copies of MCL-1 were observed (Fig. ). The fact that the 2:2 complex was observed and the coiled coil alone is absent from the mass spectra suggest that MCL-1:MCL-1 interactions aid in complex stabilisation.