Total solid-phase synthesis of bombesin analogs with different functional groups at the C-terminus.

Five bombesin analogs with different functional groups at the C-terminus were synthesized using a solid-phase strategy. The protocols were optimized using 4-(hydroxymethyl)benzoic acid (HMBA) resin to synthesize a common precursor followed by nucleophilic cleavage of the base sensitive peptide ester linkage. The C-terminal modifications included ethylamide, butylamide, methyl ester, propyl ester and hydrazide. Cleavage from the resin was possible with the fully protected or deprotected precursor peptide; however, higher purity of the final products was achieved when cleavage protocols were conducted after side-chain deprotection. The synthesized peptides were analyzed and characterized using reverse phase HPLC and ESI-MS. The peptides were obtained in 13-32% overall recovery, calculated from the coupling efficiency of the first amino acid residue, and in 91-97% purity.