Targeting the early oligomerization of amyloid $\beta$ protein (A$\beta$) is a promising therapeutic strategy for Alzheimer's disease (AD). Recently, certain C-terminal fragments (CTFs) derived from A$\beta$42 were shown to be potent inhibitors of A$\beta$-induced toxicity. The shortest peptide studied, A$\beta$(39-42), has been shown to modulate A$\beta$ oligomerization and inhibit A$\beta$ toxicity. Understanding the mechanism of these CTFs, especially A$\beta$(39-42), is of significance for future therapeutic development of AD and peptidomimetic-based drug development. Here we used ion mobility spectrometry-mass spectrometry to investigate the interactions between two modified A$\beta$(39-42) derivatives, VVIA-NH2 and Ac-VVIA, and full-length A$\beta$42. VVIA-NH2 was previously shown to inhibit A$\beta$ toxicity, whereas Ac-VVIA did not. Our mass spectrometry analysis revealed that VVIA-NH2 binds directly to A$\beta$42 monomer and small oligomers while Ac-VVIA binds only to A$\beta$42 monomer. Ion mobility studies showed that VVIA-NH2 modulates A$\beta$42 oligomerization by not only inhibiting the dodecamer formation but also disaggregating preformed A$\beta$42 dodecamer. Ac-VVIA also inhibits and removes preformed A$\beta$42 dodecamer. However, the A$\beta$42 sample with the addition of Ac-VVIA clogged the nanospray tip easily, indicating that larger aggregates are formed in the solution in the presence of Ac-VVIA. Molecular dynamics simulations suggested that VVIA-NH2 binds specifically to the C-terminal region of A$\beta$42 while Ac-VVIA binds dispersedly to multiple regions of A$\beta$42. This work implies that C-terminal interactions and binding to A$\beta$ oligomers are important for C-terminal fragment inhibitors.