103321-51-3Relevant articles and documents
Orthogonal 19F-Labeling for Solid-State NMR Spectroscopy Reveals the Conformation and Orientation of Short Peptaibols in Membranes
Grage, Stephan L.,Kara, Sezgin,Bordessa, Andrea,Doan, Véronique,Rizzolo, Fabio,Putzu, Marina,Kuba?, Tomá?,Papini, Anna Maria,Chaume, Grégory,Brigaud, Thierry,Afonin, Sergii,Ulrich, Anne S.
, p. 4328 - 4335 (2018)
Peptaibols are promising drug candidates in view of their interference with cellular membranes. Knowledge of their lipid interactions and membrane-bound structure is needed to understand their activity and should be, in principle, accessible by solid-state NMR spectroscopy. However, their unusual amino acid composition and noncanonical conformations make it very challenging to find suitable labels for NMR spectroscopy. Particularly in the case of short sequences, new strategies are required to maximize the structural information that can be obtained from each label. Herein, l-3-(trifluoromethyl)bicyclopent[1.1.1]-1-ylglycine, (R)- and (S)-trifluoromethylalanine, and 15N-backbone labels, each probing a different direction in the molecule, have been combined to elucidate the conformation and membrane alignment of harzianin HK-VI. For the short sequence of 11 amino acids, 12 orientational constraints have been obtained by using 19F and 15N NMR spectroscopy. This strategy revealed a β-bend ribbon structure, which becomes realigned in the membrane from a surface-parallel state towards a membrane-spanning state, with increasing positive spontaneous curvature of the lipids.
A new facile one-pot preparation of pentafluorophenyl (Pfp) and 3,4-dihydro-4-oxo-1,2,3-benzotriazine-3-yl (Dhbt) esters of Fmoc amino acids
Jacobsen, Mogens Havsteen,Buchardt, Ole,Engdahl, Tom,Holm, Arne
, p. 6199 - 6202 (1991)
A new one-pot procedure for the preparation of pentafluorophenyl and 3,4-dihydro-4-oxo-1,2,3-benzotriazine-3-yl esters of Nα-9-fluorenylmethyloxycarbonyl amino acids bearing no side chain protecting groups is described. The method gives the desired activated esters in high yield and purity without use of the highly allergenic DCC.
N-Amination Converts Amyloidogenic Tau Peptides into Soluble Antagonists of Cellular Seeding
Del Valle, Juan R.,Lin, Yu-Shan,Makwana, Kamlesh M.,Miao, Jiayuan,Sarnowski, Matthew P.
, p. 3928 - 3938 (2021/10/29)
The spread of neurofibrillary tangles composed of tau protein aggregates is a hallmark of Alzheimer's and related neurodegenerative diseases. Early oligomerization of tau involves conformational reorganization into parallel β-sheet structures and supramolecular assembly into toxic fibrils. Despite the need for selective inhibitors of tau propagation, β-rich protein assemblies are inherently difficult to target with small molecules. Here, we describe a minimalist approach to mimic the aggregation-prone modules within tau. We carried out a backbone residue scan and show that amide N-amination completely abolishes the tendency of these peptides to self-aggregate, rendering them soluble mimics of ordered β-strands from the tau R2 and R3 domains. Several N-amino peptides (NAPs) inhibit tau fibril formation in vitro. We further demonstrate that NAPs 12 and 13 are effective at blocking the cellular seeding of endogenous tau by interacting with monomeric or fibrillar forms of extracellular tau. Peptidomimetic 12 is serum stable, non-toxic to neuronal cells, and selectivity inhibits the fibrilization of tau over Aβ42. Structural analysis of our lead NAPs shows considerable conformational constraint imposed by the N-amino groups. The described backbone N-amination approach provides a rational basis for the mimicry of other aggregation-prone peptides that drive pathogenic protein assembly.
Total synthesis and structure elucidation of JBIR-39: A linear hexapeptide possessing piperazic acid and γ-hydroxypiperazic acid residues
Yoshida, Masahito,Sekioka, Naoki,Izumikawa, Miho,Kozone, Ikuko,Takagi, Motoki,Shin-ya, Kazuo,Doi, Takayuki
, p. 3031 - 3041 (2015/02/05)
The total synthesis and stereochemical structural elucidation of JBIR-39, containing four nonproteinogenic piperazic acid (Piz) residues, is reported. The synthesis includes Sc(OTf)3-catalyzed acylation of a Piz(γ-OTBS) derivative with piperazi
