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. 2017 Mar 30:8:14882.
doi: 10.1038/ncomms14882.

Sequence-selective encapsulation and protection of long peptides by a self-assembled FeII8L6 cubic cage

Jesús Mosquera  1 , Bartosz Szyszko  1 , Sarah K Y Ho  1 , Jonathan R Nitschke  1
Affiliations

Sequence-selective encapsulation and protection of long peptides by a self-assembled FeII8L6 cubic cage

Jesús Mosquera et al. Nat Commun. .

Abstract

Self-assembly offers a general strategy for the preparation of large, hollow high-symmetry structures. Although biological capsules, such as virus capsids, are capable of selectively recognizing complex cargoes, synthetic encapsulants have lacked the capability to specifically bind large and complex biomolecules. Here we describe a cubic host obtained from the self-assembly of FeII and a zinc-porphyrin-containing ligand. This cubic cage is flexible and compatible with aqueous media. Its selectivity of encapsulation is driven by the coordination of guest functional groups to the zinc porphyrins. This new host thus specifically encapsulates guests incorporating imidazole and thiazole moieties, including drugs and peptides. Once encapsulated, the reactivity of a peptide is dramatically altered: encapsulated peptides are protected from trypsin hydrolysis, whereas physicochemically similar peptides that do not bind are cleaved.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Synthesis and views of 1.
(a) The one-pot synthetic procedure leading from 6 equiv. of porphyrin A, 24 equiv. of tetrahydronaphthylamine B and 8 equiv. of iron(II) trifluoromethanesulfonate to cube 1. Only one face of the cube is shown in ball-and-stick form for clarity. (b) Ball-and-stick representations of three different MM2 energy-minimized models of 1 (not showing hydrogen atoms), having void volumes (shown in yellow) of 10,083, 5,600 and 3,143 Å3, respectively, the range of which is attributed to the flexibility of 1. The fused cyclic parts of the aniline residues are omitted for clarity in (b). DMF, dimethylformamide; OTf, trifluoromethanesulfonate.
Figure 2
Figure 2. Trypsin treatment of peptides G8 and G9 in the presence and absence of 1.
The yield of cleavage for each peptide is shown below the fragments. Arrows indicate the position where peptides are cleaved. Abz, 2-aminobenzoic acid; Dnp, 2,4-dinitrophenyl.
See this image and copyright information in PMC

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