Previously， we discovered and structurally characterized a complex between amyloid β 1-40 and the neuropeptide leucine enkephalin. This work identified leucine enkephalin as a potentially useful starting point for the discovery of peptide-related biotherapeutics for Alzheimer's disease. In order to better understand such complexes that are formed in vitro， we describe here the analysis of a series of site-directed amino acid substitution variants of both peptides， covering the leucine enkephalin sequence in its entirety and a large number of selected residues of amyloid β 1-40 (residues: D1， E3， F4， R5， H6， Y10， E11， H13， H14， Q15， K16， E22， K28， and V40). Ion mobility-mass spectrometry measurements and molecular dynamics simulations reveal that the hydrophobic C-terminus of leucine enkephalin (Phe-Leu， FL) is crucial for the formation of peptide complexes. As such， we explore here the interaction of the dipeptide FL with both wildtype and variant forms of amyloid β in order to structurally characterize the complexes formed. We find that FL binds preferentially to amyloid β oligomers and attaches to amyloid β within the region between its N-terminus and its hydrophobic core， most specifically at residues Y10 and Q15. We further show that FL is able to prevent fibril formation.