Three-Dimensional Structural Control of Diastereomeric Leu-Leu-Aib-Leu-Leu-Aib Sequences in the Solid State

Three diastereomeric -Leu-Leu-Aib-Leu-Leu-Aib- peptides composed of the same numbers of l-Leu, d-Leu, and Aib residues were synthesized: Boc-l-Leu-l-Leu-Aib-d-Leu-d-Leu-Aib-OMe (<b>1</b>), Boc-l-Leu-d-Leu-Aib-l-Leu-d-Leu-Aib-OMe (<b>2</b>), and Boc-l-Leu-d-Leu-Aib-d-Leu-l-Leu-Aib-OMe (<b>3</b>). The crystals of the three peptides were characterized by X-ray crystallographic analysis as follows: (<b>1</b>) orthorhombic, <i>P</i>2<sub>1</sub>2<sub>1</sub>2<sub>1</sub>, <i>a</i> = 21.383 Å, <i>b</i> = 11.070 Å, <i>c</i> = 19.560 Å, <i>Z</i> = 4, <i>R</i><sub>1</sub> = 0.0527, and <i>R</i><sub><i>w</i></sub> = 0.1562; (<b>2</b>) monoclinic, <i>P</i>2<sub>1</sub>, <i>a</i> = 9.391 Å, <i>b</i> = 21.278 Å, <i>c</i> = 11.662 Å, β = 99.125, <i>Z</i> = 2, <i>R</i><sub>1</sub> = 0.0507, and <i>R</i><sub><i>w</i></sub> = 0.1447; and (<b>3</b>) triclinic, <i>P</i>1, <i>a</i> = 12.545 Å, <i>b</i> = 14.913 Å, <i>c</i> = 15.330 Å, α = 77.622, β = 66.601, γ = 78.839, <i>Z</i> = 2, <i>R</i><sub>1</sub> = 0.0775, and <i>R</i><sub><i>w</i></sub> = 0.1971. The three diastereomeric peptides, <b>1</b>, <b>2</b>, and <b>3</b>, showed unique conformations. That is to say, <b>1</b> was folded into a left-handed (<i>M</i>) 3<sub>10</sub>-helical structure, <b>2</b> was folded into a distorted β-hairpin nucleated by a type II′ β-turn-like structure, and <b>3</b> was folded into an S-shape turn structure based on two type II/III β-turns.