MODULAR DESIGN OF SYNTHETIC PROTEIN MIMICS - CRYSTAL-STRUCTURES, ASSEMBLY, AND HYDRATION OF 2 15-RESIDUE AND 16-RESIDUE APOLAR, LEUCYL-RICH HELICAL PEPTIDES

Two 15- and 16-residue peptides containing-αminoisobutyric acid (Aib) have been synthesized, as part of a strategy to construct stereochemically rigid peptide helices, in a modular approach to design of protein mimics. The peptides Boc-(Val-Ala-Leu-Aib)4-OMe (I) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib)2-OMe (II) have been crystallized. Both crystals are stable only in the presence of mother liquor or water. The crystal data are as follows. I: 078]4 60, 92 20, P2t, a = 16.391 (3) A, b = 16.860 (3) A, c = 18.428 (3) A, β = 103.02 (1)°, Z = 2, R = 9.6% for 3445 data with |F0| > 3σ(F), resolution 0.93 A. II: C74H133N15O18-7.5H2O, C2221 a = 18.348 (5) A, b = 47.382 (11) A, c = 24.157 (5) A, Z = 8, R = 10.6%-for 3147 data with |F0| > 3σ(F), resolution 1.00 A. The 15-residue peptide (II) is entirely a helical, while the 16-residue peptide (I) has a short segment of 310 helix at the N terminus. The packing of the helices in the crystals is rather inefficient with no particular attractions between Leu-Leu side chains, or any other pair. Both crystals have fairly large voids, which arc filled with water molecules in a disordered fashion. Water molecule sites near the polar head-to-tail regions are well determined, those closer to the hydrophobic side chains less so and a number of possible water sites in the remaining “empty” space are not determined. No interdigitation of Leu side chains is observed in the crystal as is hypothesized in the “leucine zipper” class of DNA binding proteins. © 1990, American Chemical Society. All rights reserved.