Peptides containing dipropylglycine. Part 1. Preparation of protected derivatives of dipropylglycine and their incorporation into dipeptides.
Methods for the incorporation of the hindered amino acid 2-amino-2-propylpentanoic acid (dipropylglycine, Dpg) into peptides have been investigated. Limitations on the preparation of protected derivatives of Dpg are discussed, and common methods of coupling examined. These methods are not subject to problems when used to link protein amino acids to the amino group of Dpg, but steric hindrance severely limits efficient peptide bond formation by the carboxyl group of Dpg. Only two reagents proved useful in this respect. N-Benzyloxycarbonyl (Z) Dpg can be coupled through its derivative with 3-hydroxy-4-oxo-3,4-dihydrobenzotriazine; other methods of activation of Z-Dpg tend to lead to formation of 2-benzyloxy-4,4-dipropyloxazolin-5(4H)-one, which resists attack by nucleophiles. 2-Trifluoromethyl-4,4-dipropyloxazolin-5(4H)-one, however, which is readily prepared from N-trifluoroacetyl-Dpg and thionyl chloride, couples cleanly with other amino acids, making it the reagent of choice for introduction of a Dpg residue.
D000495:Allosteric Site; D004151:Dipeptides / Q000138:chemical synthesis*; D008722:Methods; D014633:Valine / Q000031:analogs & derivatives*
D004151:Dipeptides; C038263:dipropylglycine; D014633:Valine