Key analogs of the tetrapeptide subunit of RA-VII and deoxybouvardin.
The synthesis and evaluation of two key analogs 3 and 4 of the potent antitumor antibiotics deoxybouvardin (1) and RA-VII (2) which contain fundamental modifications in the tetrapeptide subunit are described. Unlike the natural products, these agents 3 and 4, which substitute (Gly)4 and (Gly)3 for the D-Ala-Ala-NMe-Tyr(OMe)-Ala tetrapeptide subunit, adopt conformations in which the central amide in the cycloisodityrosine subunit adopts its inherently preferred trans stereochemistry and both were found to be biologically inactive.
Boger
D L
DL
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Zhou
J
J
Winter
B
B
Kitos
P A
PA
D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D010456:Peptides, Cyclic; C043547:RA V; C043548:RA VII