Anginex is a designed peptide 33mer that functions as a cytokine-like agent to inhibit angiogenesis. Although this short linear peptide has been shown by NMR and CD to form a nascent beta-sheet conformation in solution, the actual bioactive structure formed upon binding to its receptor on the surface of endothelial cells could be quite different. By using a series of double-cysteine disulphide-bridged analogues, we provide evidence in the present study that the beta-sheet is in fact the bioactive conformation of anginex. CD and NMR spectral analysis of the analogues indicate formation of a beta-sheet conformation. Three functional assays, endothelial cell proliferation, apoptosis and in vitro angiogenesis, were performed on all analogues. As long as the placement of disulphide bonds preserved the beta-strand alignment, as in the proposed bioactive conformation, bioactivities were preserved. Knowledge of the bioactive conformation of anginex will aid in the design of smaller molecule mimetics of this potent anti-angiogenic peptide.

Anginex, a designed peptide 33mer, is known to function both as an antiangiogenic and bactericidal agent. Solving the NMR solution structure of the peptide is key to understand better its structureactivity relationships and to design more bioactive peptides and peptide mimetics. However, structure elucidation of anginex has been elusive due to subunit exchange-induced resonance broadening. Here, we found that performing NMR structural studies in a micellar environment abolishes exchange broadening and allows the structure of anginex to be determined. Anginex folds in an amphipathic, three-stranded antiparallel β-sheet conformation with functionally key hydrophobic residues lying on one face of the β-sheet and positively charged, mostly lysine residues, lying on the opposite face. Structural comparison is made with a homologous, yet relatively inactive peptide, βpep-28. These results contribute to the design of peptidomimetics of anginex for therapeutic use against angiogenically-related diseases like cancer, as well as infectious diseases.

A map of melon (Cucumis melo L.) with 411 markers (234 RFLPs, 94 AFLPs, 47 RAPDs, 29 SSRs, five inter-SSRs, and two isozymes) and one morphological trait (carpel number) was constructed using the F2 progeny of a cross between the Korean accession P1161375 and the Spanish melon type 'Pinyonet Piel de Sapo'. RFLPs were obtained using 212 probes from different genomic and cDNA melon libraries, including 16 Arabidopsis ESTs, 13 Cucumis known genes, and three resistant gene homologues. Most loci (391) mapped to 12 major linkage groups, spanning a total genetic distance of 1197 cM, with an average map interval of 3 cM/marker. The remaining 21 loci (six RAPDs and 15 AFLPs) were not linked. A majority (66%) of the markers were codominant (RFLPs, SSRs, and isozymes), making them easily transferable to other melon crosses. Such markers can be used as a reference, to merge other melon and cucumber maps already constructed. Indeed, some of them (23 SSRs, 14 RFLPs, one isozyme, and one morphological trait) could act as anchor points with other published cucurbit maps.

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