Planta Med 2010; 76 - P177
DOI: 10.1055/s-0030-1264475

New cystine knot peptides from a marine sponge Asteropus sp.

J Jung 1, H Li 1, J Li 1, C Lee 2, W Lee 3, C Sim 4, J Hong 5
  • 1Pusan National University, College of Pharmacy, Geumjeong-gu, 609735 Busan, Korea, Republic Of
  • 2Korea Research Institute of Chemical Technology, Daejon, 609–735 Daeojon, Korea, Republic Of
  • 3KRIBB, Bioindustry Research Center, Jeongeup, 580–185 Jeongeup, Korea, Republic Of
  • 4Hannam University, Daejon, 306–791 Daejon, Korea, Republic Of
  • 5Kyung Hee University, College of Pharmacy, Seoul, 130–701 Seoul, Korea, Republic Of

Four novel peptides 1–4 were isolated from a marine sponge Asteropus sp., collected off the coast of Geoje Island, Korea. The primary structures of the peptides were determined by automated Edman degradation and corroborated by MALDI-TOF MS spectrometry. Six Cys residues in each peptide formed three intramolecular disulfide bonds and arranged in the pattern -C-C-CC-C-C-, which characterizes the cystine knot peptides similar to some conotoxins and spider toxins. The solution structures of the peptides by 1D and 2D NMR revealed the N-terminus of each peptide to be blocked by a pyroglutamic acid. Unlike the common cystine knot peptides, each peptide exhibited highly negative charge, which might contribute to different biological functions. Peptide 1 exhibited moderate suppressive effects on NO production at the concentration of 100µM without significant cytotoxicity against the cells. In the neuraminidase inhibition assay, 1 showed mild activity with IC50 value of 181.69µM.

Table 1: Cystine knot peptides from a sponge Asteropus sp.

a Sequence identity compared to ABU8–1

Peptide

Sequence

Isoelectric point

Charge

Identity (%)a

ABU8–1

pEGCAFEGESCNVQFYPCCPGLGLTCIPGNPDGTCYYL

3.33

–4

100

ABU8–2

pEGCAFEGESCNVEFYPCCPGLGLTCIPGNPDGTCYYL

3.26

–5

97

ABU8–3

pEDCPGEGEQCDVEFNPCCPPLTCIPGDPYGICYII

3.09

–7

59

ABU8-a

pEGCAGPGEECIVGFYDCCPGYRCYPGDPGGICY

3.64

–4

60