Metal-Coordinated Supramolecular Polymers from the Minimalistic Hybrid Peptide Foldamers.

Availing the peptide folded architectures to design metal-coordinated frameworks and cages is restricted due to the scarcity of readily accessible short and stable secondary structures. The secondary structures, α-helix and ß-sheets, play significant roles in stabilizing tertiary folds of proteins. Designing such helical structures from the short sequences of peptides without having any steric restrictions is exceptionally challenging. Here we reveal the short α,γ-hybrid tripeptide sequences that manifest stable helical structures without having any sterically constrained amino acids. These short hybrid tripeptides fold into helices even in the presence of two typically ß-sheet favoring Val residues. The hybrid helix consisting of terminal pyridine units coordinates with the metal ions and drives the helical polymerization. Depending on the sequence and the position of N in pyridine moieties, these peptides form selective metallogels with Ag+ and Cu2+ ions. The X-ray diffracted analysis of the peptide single crystals obtained from the gel matrix reveals that the helical structure is maintained during the self-assembly process. Further, by varying the counter anion, a 3D helical crystalline coordination polymer with permanent porosity is generated. The findings reported here can be used to design new functional metal-foldamer coordinated polymers.

Ambidextrous α,γ-Hybrid Peptide Foldamers.

Molecular chirality is ubiquitous in nature. The natural biopolymers, proteins and DNA, preferred a right-handed helical bias due to the inherent stereochemistry of the monomer building blocks. Here, we are reporting a rare co-existence of left- and right-handed helical conformations and helix-terminating property at the C-terminus within a single molecule of α,γ-hybrid peptide foldamers composed of achiral Aib (α-aminoisobutyric acid) and 3,3-dimethyl-substituted γ-amino acid (Adb; 4-amino-3,3-dimethylbutanoic acid). At the molecular level, the left- and right-handed helical screw sense of α,γ-hybrid peptides are representing a macroscopic tendril perversion. The pronounced helix-terminating behaviour of C-terminal Adb residues was further explored to design helix-Schellman loop mimetics and to study their conformations in solution and single crystals. The stereochemical constraints of dialkyl substitutions on γ-amino acids showed a marked impact on the folding behaviour of α,γ-hybrid peptides.

Metal-Helix Frameworks from Short Hybrid Peptide Foldamers.

The potential of structured peptides has not been explored much in the design of metal-organic frameworks (MOFs). This is partly due to the difficulties in obtaining stable secondary structures from the short α-peptide sequences. Here we report the design, crystal conformations, coordination site dependent different silver coordinated frameworks of short α,γ-hybrid peptide 12-helices consisting of terminal pyridyl moieties and the utility of metal-helix frameworks in the adsorption of CO2 . Upon silver ion coordination the 12-helix terminated by the 3-pyridyl derivatives adopted a 2:2 macrocyclic structure, while the 12-helix terminated by the 4-pyridyl derivatives displayed remarkable porous metal-helix frameworks. Both head-to-tail intermolecular H-bonds of the 12-helix and metal ion coordination have played an important role in stabilizing the ordered metal-helix frameworks. The studies described here open the door to design a new class of metal-organic-frameworks from peptide foldamers.

Structural Dimorphism of Achiral α,γ-Hybrid Peptide Foldamers: Coexistence of 12- and 15/17-Helices.

Here, novel 12-helices in α,γ-hybrid peptides composed of achiral α-aminoisobutyric acid (Aib) and 4-aminoisocaproic acid (Aic, doubly homologated Aib) monomers in 1:1 alternation are reported. The 12-helices were indicated by solution and crystal structural analyses of tetra- and heptapeptides. Surprisingly, single crystals of the longer nonapeptide displayed two different helix types: the novel 12-helix and an unprecedented 15/17-helix. Quantum chemical calculations on both helix types in a series of continuously lengthened Aib/Aic-hybrid peptides confirm that the 12-helix is more stable than the 15/17-helix in shorter peptides, whereas the 15/17-helix is more stable in longer sequences. Thus, the coexistence of both helix types can be expected within a definite range of sequence lengths. The novel 15/17- and 12-helices in α,γ-hybrid peptides with 5→1 and 4→1 hydrogen-bonding patterns, respectively, can be viewed as backbone-expanded analogues of native α- and 310 -helices.