Peptides ligation, chemoselective

Chemoselective ligation of peptides using the free amino terminal as nucleophile and a thiobenzyl thioester C-terminal amino acid as electrophile provides an efficient approach to the synthesis of proteins with several hundred residues [30]. From this perspective the introduction of non-natural amino acids into proteins becomes a possibility rather than a problem and chemoselective ligation is thus a prospect for the future for the incorporation of new functionality. 

Fig. 13. Reaction mechanism of 33-residue amphiphilic helix catalyzed chemoselective ligation of hehcal peptides. The fimction of the catalyst is to organize the amphiphihc peptide reactants by hydrophobic forces on the smdace of the folded helix...

Amino acid derivatives and symmetric derivatization of (3-cyclodextrin that allows the selective replacement of all the primary hydroxy groups are predominant in literature but compared to a- and y-cyclodextrin, (3-cyclodextrin exhibits a rather low water solubility.174 In view of the methodology of chemoselective ligation, which allows the condensation of completely unprotected peptide fragments in aqueous buffer solution, symmetric derivatization of a- and y-cyclodextrin should be favorable. 28 ... 

The chemoselective ligation approach of thioester bond formation for the preparation of complex peptides has been used in a straightforward, convenient synthesis of a four-helix-bundle TASP molecule. Due to unique, mutually reactive functionalities, i.e. a-COSH and BrCH2COOH, the reaction of the unprotected peptide fragments proceeds rapidly in aqueous solution to give a homogeneous product in high yield. 18 ... 

Another versatile chemoselective ligation method for the efficient synthesis of TASP[98] molecules is based on the rapid and selective reaction of thiols with activated double bonds, e.g. in a maleimide group (Scheme 17).[106-108] For this purpose, the cyclic decameric template is functionalized with four maleimide residues, which allow reaction with thiol-containing peptide fragments in aqueous solution. 

I. Shin, H.-J. Jung, and M.-R. Lee, Chemoselective ligation of maleimidosugars to peptides/ protein for the preparation of neoglycopeptides/neoglycoprotein, Tetrahedron Lett., 42 (2001) 1325-1328. 

Key Words Peptide microarrays small-molecule microarrays small-molecule immobilization peptide immobilization chemoselective ligation. 

Zeng, W., Ghosh, S., Macris, M Pagnon, J., and Jackson, D.C. (2001) Assembly of synthetic peptide vaccines by chemoselective ligation of epitopes influence of different chemical linkages and epitope orientations on biological activity. Vaccine 19(28-29), 3843-3852. 

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