This indicates that major determinants controlling antifungal potency as well as morphogenicity reside within the c-core motif of each defensin. However, it is also clear that this motif by itself does not contain all requirements for the morphogenic effects of BMS-907351 c-Met inhibitor MsDef1 since the GMA1-C peptide, containing this motif plus the carboxy-terminal 6 amino acids, failed to induce hyperbranching of fungal hyphae. Our previous study demonstrated that the amino-terminal 15 residues also had some contribution to the antifungal activity of MsDef1. It is therefore likely that sequences outside the c-core motif of MsDef1 are also required to produce the observed morphological changes in the fungal growth. The 15 amino-terminal residues of MsDef1 may contain additional determinants of antifungal activity and thus, together with c-core motif, may exhibit more potent antifungal activity. It will also be interesting to determine if replacement of the c-core motif of MtDef4 with that of MsDef1 will enable MtDef4 to exhibit morphogenicity and antifungal activity typical of MsDef1. The DFggcs1 mutant that lacks plasma membrane sphingolipid GlcCer and exhibits resistance to MsDef1 became sensitive to MsDef1-c4 indicating that the c-core motif of MsDef1, directly or indirectly, governs its interaction with GlcCer. That the antifungal activity of MsDef1 and MtDef4 is concentrated largely in the b2�Cb3 strands and the interposed loop was further confirmed by our observation that chemically synthesized peptides, GMA1-C and GMA4-C, containing these ccore sequences plus the carboxy-terminal 6 amino acids of each defensin exhibited strong in vitro antifungal activity against F. graminearum. Similar results were obtained previously with the radish defensin, RsAFP2, whose antifungal activity also resides mainly in the b2�Cb3 loop which contains the predicted c-core motif of this defensin. Interestingly, the homology model of MsDef1 and the NMR structure of a plant defensin NaD1 had also previously predicted a putative effector site in their b2�Cb3 loop regions. It is worth noting however that the antifungal activity of GMA1-C or GMA4-C was less potent than that of native defensin again confirming that some determinants of antifungal activity reside outside the c-core motifs. Although chemically synthesized GMA1-C and GMA4-C peptides each contained four cysteines, molecular mass of these peptides indicated no formation of a BAY-60-7550 non-native disulfide bond formation. The possibility that non-native disulfide bonds might have been formed during the interaction of these peptides with the fungus could not be ruled out. Further studies were carried out to delineate the minimal amino acid sequence required for the antifungal activity of the active regions of MsDef1 and MtDef4.