UNIGE document Scientific Article
previous document  unige:135871  next document
add to browser collection
Title

Peptide Stapling with Anion‐π Catalysts

Authors
Published in Chemistry (Asian Journal). 2020, vol. 15, no. 10, p. 1562-1566
Abstract We report design, synthesis and evaluation of a series of naphthalenediimides (NDIs) that are bridged with short peptides. Reminiscent of peptide stapling technologies, the macrocycles are conveniently accessible by a chromogenic nucleophilic aromatic substitution of two bromides in the NDI core with two thiols from cysteine sidechains. The dimension of core‐bridged NDIs matches that of one turn of an α helix. NDI‐stapled peptides exist as two, often separable atropisomers. Introduction of tertiary amine bases in amino‐acid sidechains above the π‐acidic NDI surface affords operational anion‐π catalysts. According to an enolate chemistry benchmark reaction, anion‐π catalysis next to peptides occurs with record chemoselectivity but weak enantioselectivity. Catalytic activity drops with increasing distance of the amine base to the NDI surface, looser homocysteine bridges, mismatched, shortened and elongated α‐helix turns, and acyclic peptide controls. Elongation of isolated turns into short α helices significantly increases activity. This increase is consistent with remote control of anion‐π catalysis from the α‐helix macrodipole.
Identifiers
Full text
Structures
Research group Groupe Matile
Citation
(ISO format)
PHAM, Anh Tuan, MATILE, Stefan. Peptide Stapling with Anion‐π Catalysts. In: Chemistry (Asian Journal), 2020, vol. 15, n° 10, p. 1562-1566. doi: 10.1002/asia.202000309 https://archive-ouverte.unige.ch/unige:135871

136 hits

86 downloads

Update

Deposited on : 2020-05-18

Export document
Format :
Citation style :