Synthesis of conformationally restricted amino acids, peptides,

Details Synthesis of conformationally restricted amino acids, peptides, Synthesis of conformationally restricted amino acids, peptides,

1996-05-29

1998-09-22

Huff, Sheela

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

4 to 5 amino acid residues in defined sequence

530331, 530333, 530334, 530338, 556136, C07K 500, C07K 700, C07K 1700

Patent

active

058115153

ABSTRACT:
A method for synthesizing conformationally restricted amino acids, peptides, and peptidomimetics by ring closing metathesis. The method includes the steps of synthesizing a peptide precursor containing first and second unsaturated C--C bonds and contacting the peptide precursor with a RCM catalyst to yield a conformationally restricted peptide. Suitable peptide precursors may contain two or more unsaturated C--C bonds. These bonds may be olefinic bonds and may be contained in first and second alkenyl groups which may be allyl groups. The RCM catalyst may be a Ruthenium or Osmium carbene complex catalyst and more specifically, a Ruthenium or Osmium carbene complex catalyst that includes a Ruthenium or Osmium metal center that is in a +2 oxidation state, has an electron count of 16, and is pentacoordinated. The method may be carried out using solid-phase-peptide-synthesis techniques. In this embodiment, the precursor, which is anchored to a solid support, is contacted with a RCM catalyst and the product is then cleaved from the solid support to yield a conformationally restricted peptide.

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