Probing the Shielding Properties of Aptameric Protective Groups

• Published in: Chemistry, an Asian journal an Asian journal, 2014-08, Vol.9 (8), p.2225-2231
• Main Authors: Bastian, Andreas A., Rodríguez-Pulido, Alberto, Gruszka, Agnieszka, Gerasimov, Jennifer Y., Herrmann, Andreas
• Format: Article
• Language: English
• Subjects: aminoglycosides; Anti-Bacterial Agents - chemistry; aptameric protective groups; aptamers; Aptamers, Nucleotide - chemistry; Base Sequence; Binding Sites; Chemistry; Framycetin - chemistry; Proton Magnetic Resonance Spectroscopy; R&D; regioselectivity; Research & development; RNA; Spectrometry, Mass, Electrospray Ionization
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201402327

Site‐specific derivatization of chemically equivalent functional groups has recently been facilitated by the introduction of high‐affinity aptamers as non‐covalent protective groups. More specifically, a series of RNA aptamers have proven to be highly efficient in enhancing the regioselectivity of reactions with the aminoglycoside antibiotic neomycin B, which carries several chemically indistinguishable amino and hydroxy groups. Since small‐molecule targets tend to exhibit multiple modes of binding with a single aptamer, the impact of secondary binding sites on the regioselectivity should be considered. To address this issue, we investigated a series of well‐characterized RNA aptamers that bind neomycin B and propose a mechanism that accounts for the regioselective outcome of these transformations. We further demonstrate that the regioselectivity induced by non‐covalent aptamer protective groups is determined by the number of binding sites, their affinity, and the mode of interaction with the guest molecule. Getting very protective: Non‐covalent aptameric protective groups may be used to control reaction regioselectivity by shielding the functional groups in contact with the aptamer during chemical modification. Secondary binding sites complicate such a protection mechanism. Here, the aptamer‐protected acylation of neomycin B is investigated and a systematic evaluation of the effect of alternative binding modes on the reaction regioselectivity is outlined.