Insertion of a Flexible Spacer Increases the Yield of Site-Specific Bioconjugation through N-Terminal Transamination

Author(s): Annj Zamuner, Giuseppe Sica, Monica Dettin*.

Journal Name: Letters in Organic Chemistry

Volume 14 , Issue 7 , 2017

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Graphical Abstract:


Background: Recently, several chemoselective techniques have been developed to modify biomolecules at a single site. Among these, biomimetic transamination reaction through pyridoxal-5- phosphate is able exclusively to convert the N-terminus of protein/peptides into a ketone/aldehyde under mild conditions. The ketone/aldehyde group can be conjugated with another biomolecule, for example, with an aminooxy group via oxime formation.

Methods: Conjugation through oxime formation between self-assembling peptides (SAPs) and different bioactive motifs were investigated. Adhesive sequences from Fibronectin (RGD) and Vitronectin (HVP) were synthesized, purified and finally condensed with SAPs carrying an aminooxy group. Each adhesive sequence was prepared with or without the insertion of a flexible spacer to the N-terminus, consisting in an additional sequence H-Gly-7aminoheptanoic acid. The influence of the spacer on both transamination reaction and bioconjugation was evaluated.

Results: The addition of a flexible spacer to the peptide improved transamination reaction’s yield (from 27% to 53% for RGD; from 8% to 25% for HVP) and determined a significant increase in oxime yield (from 0÷3% to 37% for RGD and from 0% to 86% for HVP).

Conclusion: The introduction of a flexible spacer in the molecule carrying the ketone/aldehyde functional group dramatically improves the yield of chemoselective oxime ligation.

Keywords: Chemoselective ligation, oxime, peptide, spacer, transamination, α-ketoaldehyde.

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Article Details

Year: 2017
Page: [479 - 482]
Pages: 4
DOI: 10.2174/1570178614666170505113703
Price: $65

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