Solid-phase synthesis of bombesin by continuous flow procedure using Fmoc-amino acids.
Bombesin has been synthesized by the continuous flow solid-phase procedure on the derivatized Kieselguhr-supported polydimethylacrylamide resin. Preformed Fmoc-amino acid symmetrical anhydrides (Met, Leu, and Arg) and Fmoc-amino acid active esters were used for amine acylation. The Mtr and the Pmc groups have been alternatively used for masking the side chain function of Arg-3. The progress of the synthesis was monitored by different analytical methods including quantitative solid-phase Edman degradation. Cleavage from the resin and simultaneous formation of the C-terminal amide function were achieved with a methanolic ammonia solution yielding indistinguishable crude peptides which have been purified by HPLC and fully characterized. Preliminary pharmacological experiments indicated that the activity of the synthetic peptides is similar to that previously measured for other synthetic bombesins. For comparison bombesin has also been prepared by solid-phase synthesis on 4-methyl benhydrylamine resin using the Boc chemistry. The results of the two strategies are discussed and compared.
Scolaro
B
B
Department of Organic Chemistry, Biopolymer Research Centre, C.N.R., Milan, Italy.
Gozzini
L
L
Rocchi
R
R
Di Bello
C
C
D000596:Amino Acids; D000641:Ammonia; D001839:Bombesin / Q000138:chemical synthesis* / Q000302:isolation & purification; D005449:Fluorenes; D006858:Hydrofluoric Acid
D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D000641:Ammonia; D001839:Bombesin; D006858:Hydrofluoric Acid