Backbone--side-chain interactions in serine. Synthesis, crystal structure and solution conformation of a linear model...

The peptide Boc-Ser-Phe-OCH3 was synthesised by a solution-phase method using the usual workup procedure. The peptide was crystallized from a 70:30 (v/v) methanol-water mixture. The crystals are monoclinic, space group P21 with a = 5.128(2), b = 17.873(2), c = 11.386(2) A, and beta = 98.03(3) degrees. The structure was determined by direct methods and refined by structure factor least-squares procedure. The final R-value for 1499 observed reflections was 0.041. The structure contains one peptide and one solvent water molecule. The peptide adopts a beta-strand-like conformation with phi 1 = -100.3(5), psi 1 = 99.9(5), phi 2 = -122.2(5), psi T2 = -172.5(6) degrees. The Ser side-chain assumes an extended conformation with chi 11 = -177.0(4) degrees. The O gamma H group of serine acts as a proton donor in an intramolecular weak hydrogen bond with (Ser) O'1 [O gamma 1 - H gamma 1 ... O'1 = 3.253(6) A]. The Phe side-chain adopts a staggered conformation with chi 1(2) = -70.9(6), chi 2,1 (2) = 88.4(7) degrees, chi 2,2(2) = -89.2(6) degrees. The water molecule generates a loop through two hydrogen bonds with O gamma 1 [OW ... O gamma 1 = 2.893(5) A] and O'2 [OW ... O'2 = 2.962(7) A] atoms. The unit-translated peptide molecules along the a-axis are held by hydrogen bonds: N1 - H1 ... O2 (chi - 1, y, z) = 2.954(4) A and N2 - H2 ... O'1 (chi + 1, y, z) = 2.897(6) A in a manner similar to those observed in parallel beta-pleated sheet structures. There is an additional interaction involving O gamma 1 and the water molecule [OW ... O gamma 1 (chi + 1, y, z) = 2.789 (4) A]. The strong NOE peak of Ci(H) ... Ni + 1 (H) and a simultaneous weak NOE peak of Ni(H) ... Ni + 1 (H) in the ROESY spectra of two-dimensional NMR in dimethyl sulfoxide indicate a beta-strand-like conformation for the peptide in solution.