5-OHKF and NorKA, Depsipeptides from a Hawaiian Collection of Bryopsis pennata: Binding Properties for NorKA to the Human Neuropeptide Y Y₁ Receptor

Abstract

Two new cyclic depsipeptides, 5-OHKF (1) and norKA (2), together with the known congeners kahalalide F (3) and isokahalalide F ((4S)- methylhexanoic kahalalide F) (4) were isolated from the green alga Bryopsis pennata. The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analysis and mass spectrometric (ESIMS) data. The absolute configuration of each amino acid of 5-OHKF (1) and norKA (2) was determined by chemical degradation and Marfey’s analysis. The biological activities of these two compounds are also reported.

Algal proteins, peptides and amino acids

“…Kahalalide F, isolated from the green algae Bryopsis pennata (Hamann and Scheuer, 1993;Hamann et al ., 1996;Gao et al ., 2009), which present potent cytotoxic activity against several solid tumor cell lines, whereas another related metabolite, kahalalide O, was an inactive inhibitor of some cancer cell growth (Horgen et al ., 2000).…”

Marine Peptide Secondary Metabolites

“…New kahalalide derivatives were also characterized directly in the green algae Bryopsis sp. (Kan et al, 1999) and B. pennata (Gao et al, 2009). To date, 24 kahalalides including 19 cyclic peptides, kahalalide A (KA), norKA, kahalalides B-F, isokahalalide F, 5-OHKF, K, kahalalides O-Q, R 1 , S 1 , R 2 , S 2 , W, Y, and five linear peptides, kahalalides G, H, J, V, X, ranging from a C 31 tripeptide to a C 77 tridecapeptide, have been isolated from the mollusks E. rufescens, E. ornata, and E. grandifolia, or from the green alga Bryopsis sp.…”

Chemistry and Biology of Kahalalides

“…NorKA ( 23 ) and KA ( 1 ) differ in only a methylene group. 23 The former contains an isobutyric acid as the fatty acid moiety and the latter a 2-methylbutyric acid. 5-OHKF ( 24 ) and KF ( 6 ) are different in one hydroxyl group.…”

“…However, it is not possible to determine the sequential position of the DL -antipodal amino acids by Marfey’s method. 14,16,18,20,23 …”

“…19 The absolute configuration of amino acids in 5-OHKF ( 24 ) was achieved by the combination of chemical hydrolysis and Marfey’s method. 23 Amino acid analysis by Marfey’s method revealed 12 amino acids: L -Orn, D - allo -Ile (two), D -Pro, L -Thr, D - allo -Thr, D -Val (three), L -Val (two), and L -Phe. A single Marfey’s analysis was not enough because there is more than one valine or threonine that has a different absolute configuration.…”