Solution synthesis of the glyco-hexapeptide sequence of the human oncofetal fibronectin defined by monoclonal antibody FDC-6.
The glyco-hexapeptide sequence H-Val-(GalNAc-alpha)Thr-His-Pro-Gly-Tyr-OH, was synthesized in solution by the segment condensation procedure and the stepwise procedure. A peracetylated, O-galactosaminyl threonine derivative was used for incorporating the glycosylated amino acid residue into the peptide chain. A consistent racemization occurred during the acylation of H-His-Pro-Gly-Tyr(Bzl)-OBzl with Z-Val-[GalNAc(Ac)3-alpha]Thr-OH by the BOP-HOBt procedure and the D-allothreonine containing glyco-hexapeptide was isolated in about 20% yield. Stepwise elongation of the C-terminal tetrapeptide with Fmoc-[GalNAc(Ac)3-alpha]Thr-OH and Z-Val-OH, in the presence of the same coupling reagents, yielded the L-threonine containing diastereoisomer without detectable racemization. A side product, the Nim-ethoxycarbonylated hexapeptide derivative, formed during the EEDQ-mediated condensation of Fmoc-[GalNAc(Ac)3-alpha]Thr-OH with the C-terminal tetrapeptide, was isolated and characterized. Preliminary studies showed that the synthetic glycohexapeptide is a good competitive inhibitor of the binding of the FDC-6 monoclonal antibody to the oncofetal fibronectin, supporting the idea that it should represent the minimum essential structure required for the FDC-6 activity.
Gobbo
M
M
C.N.R., Department of Organic Chemistry, University of Padova, Italy.
Biondi
L
L
Filira
F
F
Rocchi
R
R
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry*; D006020:Glycopeptides / Q000138:chemical synthesis*; D006801:Humans; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D005353:Fibronectins; D006020:Glycopeptides; C031192:oncofetal antigens