16257-32-2Relevant articles and documents
N -Amino peptide scanning reveals inhibitors of Aβ42 aggregation
Tillett, Khalilia C.,Del Valle, Juan R.
, p. 14331 - 14336 (2020/04/23)
The aggregation of amyloids into toxic oligomers is believed to be a key pathogenic event in the onset of Alzheimer's disease. Peptidomimetic modulators capable of destabilizing the propagation of an extended network of β-sheet fibrils represent a potential intervention strategy. Modifications to amyloid-beta (Aβ) peptides derived from the core domain have afforded inhibitors capable of both antagonizing aggregation and reducing amyloid toxicity. Previous work from our laboratory has shown that peptide backbone amination stabilizes β-sheet-like conformations and precludes β-strand aggregation. Here, we report the synthesis of N-aminated hexapeptides capable of inhibiting the fibrillization of full-length Aβ42. A key feature of our design is N-amino substituents at alternating backbone amides within the aggregation-prone Aβ16-21 sequence. This strategy allows for maintenance of an intact hydrogen-bonding backbone edge as well as side chain moieties important for favorable hydrophobic interactions. An N-amino scan of Aβ16-21 resulted in the identification of peptidomimetics that block Aβ42 fibrilization in several biophysical assays.
Access to Enantiopure α-Hydrazino Acids for N-Amino Peptide Synthesis
Kang, Chang Won,Sarnowski, Matthew P.,Elbatrawi, Yassin M.,Del Valle, Juan R.
, p. 1833 - 1841 (2017/02/10)
Backbone N-methylation of α-peptides has been widely employed to enhance the bioavailability and bioactivity of parent sequences. Heteroatomic peptide amide substituents have received less attention due, in part, to the lack of practical synthetic strategies. Here, we report the synthesis of α-hydrazino acids derived from 19 out of the 20 canonical proteinogenic amino acids and demonstrate their use in the solid-phase synthesis of N-amino peptide derivatives.
N-amination of amino acids and its derivatives using N-Boc-O-tosyl hydroxylamine as an efficient NH-Boc transfer reagent: Electrophilic amination
Baburaj, Thankappan,Thambidurai, Sivalingam
experimental part, p. 2292 - 2294 (2012/07/17)
Terminal tert-butyloxycarbonyl (Boc) protected hydrazino acids, useful intermediates for modified peptides and biologically active heterocyclic derivatives, were synthesized by electrophilic amination methodology using N-Boc-O-tosyl hydroxylamine as an ef
