BACKBONE-SIDE-CHAIN INTERACTIONS IN SERINE - SYNTHESIS, CRYSTAL-STRUCTURE AND SOLUTION CONFORMATION OF A LINEAR-MODEL PEPTIDE N-BOC-L-SER-L-PHE-OCH3

The peptide Boc-Ser-Phe-OCH3 was synthesised by a solution-phase metho d using the usual workup procedure. The peptide was crystallized from a 70:30 (v/v) methanol-water mixture. The crystals are monoclinic, spa ce group P2(1) with a=5.128(2), b=17.873(2), c=11.386(2) Angstrom, and beta=98.03(3)degrees. The structure was determined by direct methods and refined by a 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(2)(T) = -172.5(6)degrees. The Ser side-chain assumes an extended conformation with chi(1)(1) = -177.0(4)degrees. The (OH)-H -gamma group of serine acts as a proton donor in an intramolecular wea k hydrogen bond with (Ser) O-1' [O-1(gamma)-H-1(gamma)... O-1'=3.253 ( 6) Angstrom]. The Phe side-chain adopts a staggered conformation with chi(2)(1)=-70.9(6), chi(2)(2,1)=88.4(7)degrees, chi(2)(2,2)=-89.2(6)de grees. The water molecule generates a loop through two hydrogen bonds with O-1(gamma) [OW ... O-1(gamma)=2.893(5) Angstrom] and O-2' [OW ... O-2'=2.962 (7) Angstrom] atoms. The unittranslated peptide molecules along the a-axis are held by hydrogen bonds: N-1-H-1 ... O-2 (x-1, y, z)=2.954(4) Angstrom and N-2-H-2 ... O-1'(x + 1, y, z) = 2.897(6) Angs trom in a manner similar to those observed in parallel beta-pleated sh eet structures. There is an additional interaction involving O-1(gamma ) and the water molecule [OW ... O-1(gamma) (x + 1, y, z) = 2.789(4) A ngstrom]. The strong NOE peak of C-i(H)... N-i+1 (H) and a simultaneou s weak NOE peak of N-i(H)... N-i+1 (H) in the ROESY spectra of two-dim ensional NMR in dimethyl sulfoxide indicate a beta-strand-like conform ation for the peptide in solution. (C) Munksgaard 1996.