Paralytic activity of (des-Glu1)conotoxin GI analogs in the mouse diaphragm

A series of 20 peptide analogs of (des‐Glu1) conotoxin GI were prepared by solid phase synthesis. The peptides were tested for their abilities to inhibit contractions in the mouse‐diaphragm‐with‐phrenic‐nerve assay. (Des‐Glu1) conotoxin has an IC50, of 2.7 × 10−7 M in this assay. Results from this assay show that total loss of paralytic activity occurs when Pro is replaced by Gly, Tyr by D‐Tyr, or Gly by D‐Phe. In most cases loss or change in length of one of the disulfide rings eliminates paralytic activity except with compound 17, which is weakly active, IC50= 7.0 × 10−5 M. Replacement of the Cys1‐Cys6 disulfide bond with an amide bond (compound 9) greatly lowers paralytic activity, IC5, = 3.7 × 10−5 M.