P-Phenylene diisothiocyanate

Peptides that contain a lysine residue, such as those generated by cleavage of proteins with trypsin, can be coupled efficiently to supports using p-phenylene diisothiocyanate, which cross-links both the e-amino groups of lysine and a-amino groups to the amino resin (aminopolystyrene gives the... 

Schiltz and Reinbolt, 1975) combined the diisothiocyanate and carbodiimide procedures to permit sequencing of peptides that lack lysine. The peptide is first coupled by its NH2-terminus to aminopolystyrene using p-phenylene diisothiocyanate. With the peptide bound to the resin, the COOH-terminal is then coupled using a carbodiimide. This procedure is reported to be useful for larger peptides that do not couple efficiently with the carbodiimide alone (Schiltz, 1975). 

Atherton et al (1976) described an acrylamide-based resin (3) having an open matrix that permits the attachment of large peptides and proteins. The resin amino groups are first activated with p-phenylene diisothiocyanate. 

Silanized glass beads have been used as solid supports. Peptides were coupled to the beads by using either carbodiimide or p-phenylene diisothiocyanate. The coupled peptides have been satisfactorily degraded, with a repetitive yield of about 92% (Previero et al., 1973 Schellenbei er et al., 1971, 1972 Wachter et al., 1973). As an example, cytochrome c from Canadida krusei was attached to this support and the degradation of over 35 residues, with a repetitive yield of 95%, was achieved. This clearly demonstrates the usefulness of such supports for longer molecules (Machleidt et al., 1973). The phenyl diisothiocyanate method has also been used for attachment of peptides to polyacrylamide supports (Atherton et al., 1976). 

From p-phenylene diisothiocyanate and two equivalents of the Pd(n) azido complex the bis-adduct is obtained in 37 % yield. Di(azido)bis(phosphine) complexes of Ni(ii) and Pt(ii) react similarly to give the corresponding bis(isothiocyanato) complexes In the reaction of azides with one equivalent each of an isocyanate and an isothiocyanate, the [3+2] cycloadducts 135 are obtainedIn the initial reaction of the azide with the isothiocyanate, a 1,3-dipol is generated by thermolysis of 134, which reacts with the isocyanate to form 135. 

Other isothiocyanates obtained by this method are phenyl isothiocyanate (65%), -phenylene diisothiocyanate (71%), p-acetylaminophenyl isothiocyanate (73%), />-ethoxyphenyl isothiocyanate (64%), and -bromophenyl isothiocyanate (55%). 

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