Efficient synthesis of an (aminooxy) acetylated-somatostatin derivative using (aminooxy)acetic acid as a 'carbonyl capture' reagent.
Owing to the high chemoselectivity between an aminooxy function and a carbonyl group, oxime ligation is one of the most preferred procedures for the preparation of peptide conjugates. However, the sensitivity of (aminooxy)acetylated peptides to ketones and aldehydes makes their synthesis and storage difficult. In our study, we established the efficient synthesis of an (aminooxy)acetylated-somatostatin derivative in the presence of free (aminooxy)acetic acid, which was used as a 'carbonyl capture' reagent in the final cleavage step. This (aminooxy)acetylated compound was further used for the chemoselective ligation (oxime bond formation) with daunorubicin and 4-fluorobenzaldehyde leading to the formation of conjugates with potential applications in targeted cancer chemotherapy and positron emission tomography.
Mezö
Gábor
G
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary. gmezo@elte.hu
Szabó
Ildikó
I
Kertész
István
I
Hegedüs
Rózsa
R
Orbán
Erika
E
Leurs
Ulrike
U
Bösze
Szilvia
S
Halmos
Gábor
G
Manea
Marilena
M
D000107:Acetylation; D000625:Aminooxyacetic Acid / Q000737:chemistry*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D015394:Molecular Structure; D013004:Somatostatin / Q000138:chemical synthesis* / Q000737:chemistry*
D000625:Aminooxyacetic Acid; D013004:Somatostatin; D003630:Daunorubicin