Cysteine peptides, cleavage

Cyclotriboroxanes as intermediates 27,158 Cysteine peptides, cleavage, selective 20, 37 suppl. 27... 

A reasonable mechanism for the iodine oxidation of 5-Trt cysteine peptides is given in Scheme 6. 45 Reaction of iodine with the divalent sulfur atom leads to the iodosulfonium ion 5 which is then transformed to the sulfenyl iodide 6 and the trityl cation. Sulfenyl iodides are also postulated as intermediates in the iodine oxidation of thiols to disulfides. The disulfide bond is then formed by disproportionation of two sulfenyl iodides or by reaction between the electrophilic sulfur atom of R -S-I and the nucleophilic S-atom of a second R -S-Trt molecule. The proposed mechanism suggests that any sulfur substitution (i.e., thiol protecting group) capable of forming a stabilized species on cleavage, such as the trityl cation, can be oxidatively cleaved by iodine. 

A general procedure for the iodine reaction in the solid phase is shown in Scheme 9. Both Boc and Fmoc chemistry can be used to assemble the linear S-protected bis-cysteine peptides and for thiol protection the well-established Acm and Trt groups are usually used. Suitable solvents for the thiol-deprotection/oxidation step by iodine to form the disulfide are CH2C12, DMF, or aqueous AcOH. The final deblocking and cleavage from the resin is carried out under standard conditions. Modification at sensitive amino acid residues caused... 

The cysteine proteases can be divided into three classes the papain-like, the caspases (and related enzymes), and the picorna viral cysteine proteases. The proposed catalytic mechanism for cysteine protease peptide cleavage is related to the serine protease mechanism but with a cysteine thiol acting as the nucleophile that attacks the scissile peptide bond carbonyl. 

Patchornik and coworkers studied the elimination reactions of S-2,4-dinitrophenyl-cysteine compounds 390, 391). The method proved suitable for the conversion of cysteine peptides into dehydroalanine peptides, in which the double bond can then be exploited as the site of attack in the specific (hydrolytic or oxidative) cleavage of the peptide 298—300). 

The macrocyclization of a peptide was carried out by nucleophihc substitution on a fluorobenzene by the sulfide group of the terminal cysteine of a pentapeptide [164]. The peptide 261 was prepared by standard SPPS and was cyclized under microwave irradiation at 50 °C for 10 min in DMF (Scheme 96). The yields of 262, after cleavage with TFA, were remarkably high for a macrocyclic peptide (70%) and also the resulting HPLC purity was very high. 

AM Felix, MH Jimenez, T Mowles, J Meienhofer. Catalytic hydrogenolysis in liquid ammonia. Cleavage of V -benzyloxycarbonyl groups from cysteine-containing peptides with terf-butyl side chain protection. Int J Pept Prot Res 11, 329, 1978. 

---