Channel‐forming,self‐assembling,bishelical amphiphilic peptides: design,synthesis and crystal structure of Py(Aibn)2, n = 2, 3, 4 |
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Authors: | D Ranganathan S Kurur AC Kunwar A V S Sarma M Vairamani IL Karle |
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Abstract: | Abstract: The design, synthesis, characterization and self‐assembling properties of a new class of amphiphilic peptides, constructed from a bifunctional polar core attached to totally hydrophobic arms, are presented. The first series of this class, represented by the general structure Py(Aibn)2 (Py = 2,6‐pyridine dicarbonyl unit; Aib = α, α′‐dimethyl glycine; n = 1–4), is prepared in a single step by the condensation of commercially available 2,6‐pyridine dicarbonyl dichloride with the methyl ester of homo oligoAib peptide (Aibn‐OMe) in the presence of triethyl amine. 1H NMR VT and ROESY studies indicated the presence of a common structural feature of 2‐fold symmetry and an NH…N hydrogen bond for all the members. Whereas the Aib3 segment in Py(Aib3)2 showed only the onset of a 310‐helical structure, the presence of a well‐formed 310‐helix in both Aib4 arms of Py(Aib4)2 was evident in the 1H NMR of the bispeptide. X‐ray crystallographic studies have shown that in the solid state, whereas Py(Aib2)2 molecules organize into a sheet‐like structure and Py(Aib3)2 molecules form a double‐stranded string assembly, the tetra Aib bispeptide, Py(Aib4)2, is organized to form a tetrameric assembly which in turn extends into a continuous channel‐like structure. The channel is totally hydrophobic in the interior and can selectively encapsulate lipophilic ester (CH3COOR, R = C2H5, C5H11) molecules, as shown by the crystal structures of the encapsulating channel. The crystal structure parameters are: 1b , Py(Aib2)2, C25H37N5O8, sp. gr. P212121, a = 9.170(1) Å, b = 16.215(2) Å, c = 20.091(3) Å, R = 4.80; 1c , Py(Aib3)2, C33H51N7O10·H2O, sp. gr. P, a = 11.040(1) Å, b = 12.367(1) Å, c = 16.959(1) Å, α = 102.41°, β = 97.29°, γ = 110.83°, R1 = 6.94; 1 da, Py(Aib4)2?et ac, C41H65N9O12?1.5H2O·C4H8O2, sp. gr. P, a = 16.064(4) Å, b = 16.156 Å, c = 21.655(5) Å, α = 90.14(1)°, β = 101.38(2)°, γ = 97.07(1)°, Z = 4, R1 = 9.03; 1db, Py(Aib4)2?amylac,C41H65N9O12?H2O ·C7H14O2, P21/c, a = 16.890(1) Å, b = 17.523(1) Å, c = 20.411(1) Å, β = 98.18 °, Z = 4, R = 11.1 (with disorder). |
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Keywords: | amyl acetate encapsulation ethyl acetate encapsulation hydrophobic channels tetrameric assembly pyridine scaffold 310‐helices |
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