MODIFICATIONS OF SOLID PHASE PEPTIDE SYNTHESIS TO OBTAIN HOMOGENEOUS OLIGOPROLINES IN HIGH YIELD
- 1 March 1980
- journal article
- research article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 15 (3), 225-235
- https://doi.org/10.1111/j.1399-3011.1980.tb02571.x
Abstract
When oligoprolines containing a [3H]proline in the 2nd residue from the carboxyl terminus are synthesized by the standard solid phase method using stepwise addition of prolines there appears, in addition to the oligoprolines, a steady increase of ninhydrin-negative, but radioactive, impurities. These impurities were N-trifluoroacetyl oligoprolines, and a substantial amount of diketopiperazine was present at the diproline stage. The trifluoroacetyl blockage of the N-termini was almost complete by the time 14 residues were added. To eliminate these side reactions, a block of Boc[3H]Pro2 was coupled to prolyl-resin in order to avoid the diprolyl-resin stage, and 25% CF3CO2H in CHCl3 was replaced by 4 N HCl in dioxane as the deprotecting reagent. These changes eliminated the formation of diketopiperazine and trifluoroacetyl impurities but a steady increase of ninhydrin-negative, radioactive, impurity was seen, reaching 22% after 3 couplings. These side reactions were traced to the neutralization step; in order to avoid them it became necessary to eliminate the neutralization step and replace it by incremental additions of Et3N during the coupling step. As a result of these modifications, homogeneous length oligoprolines were obtained upon cleavage from the resin, with no further purification, when analyzed by reversed-phase liquid chromatography.Keywords
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