Oligopeptides with Equal Amounts of l- and d‑Amino Acids May Prefer a Helix Screw Sense

Abstract

We investigated the preferred conformations of two nonapeptides, Boc-(l-Leu-d-Leu-Aib)₃-OMe (<b>2</b>) and its enantiomer Boc-(d-Leu-l-Leu-Aib)₃-OMe (<i>ent</i>-<b>2</b>), four dodecapeptides, Boc-(l-Leu-d-Leu-Aib)₄-OMe (<b>3</b>), Boc-(l-Leu-Aib-d-Leu)₄-OMe (<b>4</b>), Boc-(Aib-l-Leu-d-Leu)₄-OMe (<b>5</b>), and Boc-(l-Leu-Aib-d-Leu-Aib)₃-OMe (<b>6</b>), and a decapeptide, Boc-l-Leu-(d-Leu-l-Leu-Aib)₃-OMe (<b>7</b>), in solution and in the crystalline state. The nonapeptide <b>2</b> formed a right-handed (<i>P</i>) α-helix, and its enantiomer <i>ent</i>-<b>2</b> formed a left-handed (<i>M</i>) α-helix. The dodecapeptides <b>3</b> and <b>5</b> were folded into (<i>P</i>) helices, and <b>4</b> formed an (<i>M</i>) helical structure. As for <b>6</b>, roughly equivalent amounts of (<i>P</i>) and (<i>M</i>) helices were observed in solution, and two (<i>M</i>) α-helices were detected in the crystalline state. Furthermore, the decapeptide <b>7</b>, which possesses four l-Leu residues and three d-Leu residues, was folded into an (<i>M</i>) α-helix