{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:09:04Z","timestamp":1785892144866,"version":"3.56.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T00:00:00Z","timestamp":1337212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p>Protoxin II is biologically active peptide containing the inhibitory cystine knot motif. A synthetic version of the toxin was generated with standard Fmoc solid phase peptide synthesis. If <jats:italic>N<\/jats:italic>\u2010methylmorpholine was used as a base during synthesis of the linear protoxin II, it was found that a significant amount of racemization (approximately 50%) was observed during the process of cysteine residue coupling. This racemization could be suppressed by substituting <jats:italic>N<\/jats:italic>\u2010methylmorpholine with 2,4,6\u2010collidine. The crude linear toxin was then air oxidized and purified. Electrophysiological assessment of the synthesized protoxin II confirmed its previously described interactions with voltage\u2010gated sodium channels. Eight other naturally occurring inhibitory knot peptides were also synthesized using this same methodology. The inhibitory potencies of these synthesized toxins on Nav1.7 and Nav1.2 channels are summarized. 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