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Synthesis of Sulfated Glycomimetics with Micromolar Affinity for Midkine

Year: 2026

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide A series of sulfated oligosaccharides (one tetra- and ten disaccharides) have been synthesized to study their interactions with midkine, a heparin-binding growth factor involved in cancer and inflammation. These compounds were prepared as glycosaminoglycan (GAG) mimetics and displayed hydrophobic groups at specific positions to enhance midkine binding. For the synthesis of the tetrasaccharide, a fluoro-assisted strategy was adopted. The use of an N -phenyltrifluoroacetimidate donor, instead of the analogous trichloroacetimidate, proved to be crucial in obtaining the desired tetramer with good yield. On the other hand, the synthesized disaccharides differed in the number of sulfates present and in the substituent at position 2 of the glucosamine unit. Fluorescence polarization competition experiments provided relative binding affinities for each glycomimetic expressed as IC 50 values. Our results indicated that all the mimetics interacted with midkine in the micromolar range, highlighting the affinity of the 4,6-di- O -sulfated disaccharides with aromatic rings on the 2-amide group (IC 50 ’s from 3.4 ± 0.8 to 4.3 ± 1.1 μM). Overall, this study offers valuable data for the design and synthesis of high-affinity midkine ligands with potential biological applications.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.6c00064

Authors: Rocío Pereira-Jaramillo, José L. de Paz, Pedro M. Nieto

Institutions: Centro de Investigaciones Científicas Isla de la Cartuja, Instituto de Investigaciones Químicas, Universidad de Sevilla

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500