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Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
Published on: November 21, 2013
Synthesis and X-ray crystal structure of the dolabellaauricularia peptide dolastatin 18
George R Pettit1, Fiona Hogan, Delbert L Herald
1Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Abstract:
A previously synthesized unit of dolastatin 10 (1), dolaphenine (Doe, 3), was converted in four steps to tripeptide 10. Subsequent condensation with carboxylic acid 11 (four steps from Meldrum's acid) provided a practical synthesis of the cancer cell growth inhibitor dolastatin 18 (2, Dhex-(S)-Leu-(R)-N-Me-Phe-Doe). The synthesis of dolastatin 18 (2) confirmed the R stereochemistry of the N-Me-Phe unit as originally assigned and unusual among amino acid components of the sea hare Dolabella auricularia. An X-ray crystal structure determination of dolastatin 18 was also completed.
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