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

• Published in: International journal of peptide and protein research Vol. 34; no. 6; p. 455
• Main Authors: Almquist, R G, Kadambi, S R, Yasuda, D M, Weitl, F L, Polgar, W E, Toll, L R
• Format: Journal Article
• Language: English
• Published: Denmark 01-12-1989
• Subjects: Amino Acid Sequence; Animals; Conotoxins; Diaphragm - drug effects; In Vitro Techniques; Male; Mice; Molecular Sequence Data; Mollusk Venoms - chemical synthesis; Mollusk Venoms - toxicity; Neuromuscular Junction - drug effects; Paralysis - chemically induced; Rats; Structure-Activity Relationship
• ISSN: 0367-8377
• DOI: 10.1111/j.1399-3011.1989.tb01394.x

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 x 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 x 10(-5) M. Replacement of the Cys1-Cys6 disulfide bond with an amide bond (compound 9) greatly lowers paralytic activity, IC50 = 3.7 x 10(-5) M.