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 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.
Almquist
R G
RG
Life Sciences Division, SRI International, Menlo Park, CA.
Kadambi
S R
SR
Yasuda
D M
DM
Weitl
F L
FL
Polgar
W E
WE
Toll
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins; D003964:Diaphragm / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000138:chemical synthesis / Q000633:toxicity*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010243:Paralysis / Q000139:chemically induced*; D051381:Rats; D013329:Structure-Activity Relationship
D020916:Conotoxins; D008978:Mollusk Venoms; C063945:conotoxin GI, des-Glu(1)-