Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224

Induction of apoptosis by cryptophycin 1, a new antimicrotubule agent

“…Our preliminary results showed that cryptophycin caused a dosedependent increase in chromatin condensation (independent of cell cycle-induced changes) in the SKOV3 cell line and DNA fragmentation in a leukemic cell line (Golakoti et al, 1995). The present work extends the preliminary studies, and the data indicate that cryptophycin 1, at picomolar concentrations, rapidly initiates apoptosis.…”

Genetic Variation of Adenylation Domains of the Anabaenopeptin Synthesis Operon and Evolution of Substrate Promiscuity

“…In addition, a number of tailoring enzymes, such as methyltransferases, epimerases, and thioesterases (TEs), lead to the modification of the synthesized product (11). It is a characteristic feature of cyanobacterial NRPS pathways that they often produce entire families of structurally related compounds co-occurring in one specific isolate, e.g., the cryptophycins (15), laxaphycins (2,13), and nostopeptolides (16). In such NRPS peptide families, structurally related amino acids, such as Val, Ile, and Leu, are found in equivalent positions of the peptides, suggesting that the A domains of these NRPS enzymes may possess a relaxed substrate specificity (19).…”

Total Synthesis of Cryptophycin A and Analogs

“…GSV 224. 5 Their data suggested that the binding site of the cryptophycins contains a hydrophobic pocket, where the C3 isobutyl group interacts favorably. To date, inversion of the C3 center has not be done.…”

“…5 This could be due to the increased steric bulk of the aryl ring. Therefore, in order to more thoroughly test this hypothesis, I will synthesize two chlorinated phenylalanine analogs.…”