Single site OH to F substitution at the termini of maltotetraose leads to significantly improved hydrolytic stability towards alpha-amylase and alpha-glucosidase relative to the natural compound. Stability enhancements of around 1 order of magnitide result from these subtle point mutations. In both scenarios, modification of the monosaccharide furthest from the site of enzymatic cleavage leads to the greatest improvement in stability, and the configuration of the fluorine-bearing stereocenter has a clear impact on catalysis. This pre-clinical evaluation provides valuable guidelines for the development of tracer candidates for non-invasive bacterial imaging.
European Research Council (ERC-2013-StG Starter Grant - Project number 336376-ChMiFluorS to RG)
Interdisciplinary Centre for Clinical Research (IZKF), Münster, Germany (Fau2/014/17)
DFG Emmy-Noether programme (KO 4116/3-2 to J.K.)
European Commission is acknowledged for an Intra-European Marie Skłodowska-Curie actions fellowship under Horizon-2020 (796089–NovInDXS, R. P.-J.)
ERC (Starter Grant 757913 to A.K.H.H.)
InstitutionWestfälische Wilhelms-Universität Münster
ORCID For Submitting Author0000-0002-3153-6065
Declaration of Conflict of InterestNo conflict of interest.