USE OF MIN-DINITROPHENYLHISTIDINE IN SOLID-PHASE SYNTHESIS OF TRICOSAPEPTIDES 124-146 OF HUMAN HEMOGLOBIN BETA CHAIN

The tricosapeptide H-Pro-Pro-Val-Gln-Ala-Ala-Tyr-Gln-Lys-Val-Val-Ala-Gly-Val-Ala-Asn-Ala-Leu-Ala-His- Lys-Tyr-His-OH, corresponding to residues 124-146 of the β chain of human hemoglobin, was synthesized by the solidphase method. The imidazole rings of the two histidine residues were protected by the dinitrophenyl group and were deprotected by the thiolysis method of Shaltiel. Crystalline Nα-t-butyl-oxycarbonyl-Nim-2,4-dinitrophenyl-L-histidine was synthesized and shown to couple rapidly and efficiently by the dicyclohexylcarbodiimide procedure. The dinitrophenyl group was stable during the subsequent synthetic steps and in the cleavage step, but could be removed cleanly at the end under mild conditions by treatment with mercaptoethanol. This promises to be a very effective way to handle histidine during solid-phase peptide synthesis. © 1969, American Chemical Society. All rights reserved.