title: Dimerization of chirally mutated Enkephalin neurotransmitters: implications for peptide and protein aggregation mechanisms.
abstract: We have probed the structures and aggregation propensities of chirally substituted [Ala(2)]-Leu-Enkephalin peptides (i.e., Leu-Enkephalin G2A) with a combination of ion-mobility spectrometry/mass spectrometry and techniques of computational chemistry. Our IMS/MS data reveal a strong correlation between the propensity to form peptide dimers and the subsequent aggregation propensity. This correlation indicates that the dimerization process is fundamental to the overall self-assembly process. Our computational data correlate a conformational conversion during the peptide association process with a reduced experimental dimer formation and subsequent aggregation propensity. Furthermore, our analysis indicates that monomer activation does not precede peptide association and thus suggests that the entire-refolding or gain-in-interaction models are more realistic accounts of the peptide self-assembly process than the monomer-conversion model. In sum, our results suggest that conformational transitions of early peptide oligomers represent bottlenecks of the peptide self-assembly process and thus highlight the importance of structurally characterizing this reaction during amyloid formation.
authors: Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
authors: Christian
authors: C
authors: Bleiholder
authors: Nicholas F
authors: NF
authors: Dupuis
authors: Michael T
authors: MT
authors: Bowers
mesh_terms: D019281:Dimerization; D004745:Enkephalins / Q000737:chemistry* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D004745:Enkephalins; D018377:Neurotransmitter Agents