CONVERGENT SOLID PHASE PEPTIDE SYNTHESIS VI: SYNTHESIS BY THE FMOC PROCEDURE WITH A MODIFIED PROTOCOL OF TWO PROTECTED SEGMENTS, SEQUENCE 5-17 AND 18-31 OF THE NEUROTOXIN II OF THE SCORPION ANDROCTONUS AUSTRALIS HECTOR.

Article abstract of DOI:10.1016/S0040-4020(01)87803-0

Synthesis of two protected peptides thirteen and fourteen residues long, sequence 5-17, i.e.Fmoc-Tyr(cHex)-Ile-Val-Asp(Bzl)-Asp(Bzl)-Val-Asn-Cys(Acm)-Thr(Bzl)-Tyr(cHex)-Phe-Cys(Acm)-Gly-OH, and 18-31, i.e.Fmoc-Arg(Tos)-Asn-Ala-Tyr(cHex)-Cys(Acm)-Asn-Glu(Bzl)-Glu(Bzl)-Cys(Acm)-Thr(Bzl)-Lys(Z)-Leu-Lys(Z)-Gly-OH, of the scorpion neurotoxin II from Androctonus australis Hector, was perfomed by the solid phase method.The hydroxymethylphenoxymethyl copoly(styrene-1 percent-divinylbenzene) type resin was used in combination with Fmoc-amino acids for both syntheses.A general protocol minimizing side reactions has been developed for the use of base labile Fmoc-α-amino protecting group.The time of reaction with piperidine (50 percent in N,N'-dimethylformamide) has been shortened to three times one minute and coupling was performed mainly in methylene chloride with just dicyclohexyl or diisopropyl-carbodiimide.The side chain protecting groups of the Fmoc-α-amino acids were of the hydrogen fluoride labile type, which permitted, after trifluoroacetic acid cleavage of the peptide to resin ester bond, obtainment of protected peptides.The crude segments, precipitated from N,N'-dimethylacetamide with water, were highly purified by HPLC and chemically characterized for future use in convergent solid phase assembling.