Converting Sequences of Aromatic Amino Acid Monomers into Functional Three‐Dimensional Structures: Second‐Generation Helical Capsules

Abstract

New codes for sequence–structure–function relationships can be elaborated in aromatic oligoamide foldamers upon varying main‐chain components. Each monomer carries its own structural and functional features and enables oligomeric sequences to be designed to encapsulate specific guests.

A Self‐Assembled Foldamer Capsule: Combining Single and Double Helical Segments in One Aromatic Amide Sequence

“…[11][12][13][14][15][16][17] These objects have until now been much smaller and far less complex than proteic receptors. Nevertheless, they share with them a vast potential for tunability: they are based on sequences whose monomers can be changed one at a time and introduced by using the same synthetic methods.…”

“…Along these lines, we have described helical capsules based on the folding of oligoA C H T U N G T R E N N U N G amide sequences of various aromatic amino acids designed in order to create a large helix diameter at the center of the sequence and narrow diameters at the end, so as to define a closed space in which bound guest molecules are completely surrounded by the helix backbone. [17] A potential drawback of this design is that binding of an elongated guest would require a multiple turn helix comprised of numerous monomers: in other words, a difficult synthetic target. We assumed that a more straightforward route to helical containers having an elongated cavity may rest on the high propensity of some aromatic amide sequences to assemble into double-stranded helices twice as long as their single helical precursors.…”

Molecular Recognition with Linear Molecules as Receptors

“…21) [71]. The 1,8-diaza-9-fluoro-2,7-anthracenedicarboxamide unit was introduced to increase the diameter of the helix.…”

“…. The structure of compound 39 and the crystal structures of its 1:1 complexes with 1,3-propanediol (left), 1,4-butanediol (middle), and 4-amino-1-butanol (right)[71].…”

Large-scale and chromatography-free synthesis of an octameric quinoline-based aromatic amide helical foldamer

“…For example, helices [5][6][7] and macrocycles 8,9 of narrow or wide diameters; double 10 , triple 11 and quadruple helices 12 ; linear strands 13 and sheets 14,15 ; and tertiary-like objects [16][17][18][19] involving several helical segments have all been produced using aromatic amide backbones. In addition, some folding patterns unknown in peptides have been generated, such as helices whose diameter varies along the sequence 20,21 or unconventional ladderlike helices 22 . This rapid progress has put aromatic amide foldamers in the spotlight, and the field is currently attracting much interest.…”