132409-92-8Relevant academic research and scientific papers
Aza-amino acids disrupt β-sheet secondary structures
McMechen, Michael A.,Willis, Evan L.,Gourville, Preston C.,Proulx, Caroline
, (2019)
Cα to N substitution in aza-amino acids imposes local conformational constraints, changes in hydrogen bonding properties, and leads to adaptive chirality at the nitrogen atom. These properties can be exploited in mimicry and stabilization of peptide secondary structures and self-assembly. Here, the effect of a single aza-amino acid incorporation located in the upper β-strand at a hydrogen-bonded (HB) site of a β-hairpin model peptide (H-Arg-Tyr-Val-Glu-Val-d-Pro-Gly-Orn-Lys-Ile-Leu-Gln-NH2) is reported. Specifically, analogs in which valine3 was substituted for aza-valine3 or aza-glycine3 were synthesized, and their β-hairpin stabilities were examined using Nuclear Magnetic Resonance (NMR) spectroscopy. The azapeptide analogs were found to destabilize β-hairpin formation compared to the parent peptide. The aza-valine3 residue was more disruptive of β-hairpin geometry than its aza-glycine3 counterpart.
((9-Fluorenylmethyl)oxy)carbonyl Amino Acid Chlorides in Solid-Phase Peptide Synthesis
Carpino, Louis A.,Chao, Hann Guang,Beyermann, Michael,Bienert, Michael
, p. 2635 - 2642 (1991)
FMOC amino acid chlorides, previously shown to be rapid-acting coupling agents in two-phase systems or in homogeneous solution, did not prove to be directly applicable to solid phase peptide synthesis due to sluggish reactivity.The problem was traced to p
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.
Benzotriazole-assisted solid-phase assembly of Leu-Enkephalin, amyloid β segment 34-42, and other "difficult" peptide sequences
Katritzky, Alan R.,Haase, Danniebelle N.,Johnsons, Jodie V.,Chung, Alfred
body text, p. 2028 - 2032 (2009/08/07)
Microwave-assisted solid-phase syntheses of six "difficult" peptides, H-VVSVV-NH2 (3), H-VVVSVV-NH2(4), H-VIVIG-OH (5), H-TVTVTV-NH2 (6), H-VKDGYI-NH2 (7), and H-VKDVYI-NH2 (8), were achieved utilizing N-(Fmoc-α-aminoacyl) benzotriazoles. Extension to the syntheses of Leu-enkephalin (9) and amyloid-β (34-42) (10) demonstrates that this strategy comprises an efficient route to new and known "difficult" peptides.
