Design, synthesis, and conformational analysis of a proposed type I β- turn mimic

Brian E. Fink, Phil R. Kym, John A. Katzenellenbogen

Research output: Contribution to journalArticlepeer-review

Abstract

In an effort to design a dipeptide structural mimic of protein and peptide β-turns, we have prepared and evaluated the conformation of derivatives of the novel, highly constrained ten-membered lactam, (3S,10S)- (6E)-2-azacyclodec-6-enone (1). A synthetic route utilizing ring closing olefin metathesis (RCM) has been used to prepare this novel ten-membered ring in high yield. X-ray crystallography and 1H NMR analysis have established that ring closure proceeds to give the trans-olefin and that 1 exists in two conformations, that of a chair-chair and chair-boat. Monte Carlo-molecular mechanics conformational searching has indicated that this ring system would be a good mimic of a type I β-turn. The synthesis of model tri- and tetrapeptide analogues based on 1 is reported. NMR studies indicate that the tetrapeptide derivatives constrain the i+1 and i+2 torsion angles to within 30°of those predicted for an ideal type I β-turn (φ1 = -82°, ψ1 = - 20°, φ2 = -107°, ψ2 = -18°) and that this conformation was shown to be stable in both hydrogen-bonding solvents as well as non-hydrogen bonding solvents at various temperatures.

Original languageEnglish (US)
Pages (from-to)4334-4344
Number of pages11
JournalJournal of the American Chemical Society
Volume120
Issue number18
DOIs
StatePublished - May 13 1998

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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