Nucleoside-based analogues of cmp-neu5ac with triazole and ether-triazole linkers for sialyltransferase targeting
Rationally designed nucleoside analogues that replace the native phosphodiester linker of the sialyltransferase substrate CMP-Neu5Ac with triazole or ether-triazole linkers. The design aims to improve stability, pharmacokinetics, and synthetic accessibility while retaining enzymatic activity, offering new building blocks for glycobiology and drug discovery research.
Overview
This solution offers two families of rationally designed nucleoside analogues based on Cytidine 5′-monophosphate N-acetylneuraminic acid (CMP-Neu5Ac), the native substrate of sialyltransferase enzymes. The compounds replace the natural phosphodiester linker with either a triazole or an ether-triazole linker, producing novel dinucleoside structures and building blocks. By swapping a chemically and enzymatically labile phosphodiester bond for a more robust heterocyclic linkage, these analogues are designed to improve compound stability, pharmacokinetic behavior, and ease of synthesis while maintaining useful activity against sialyltransferases.
These analogues are relevant to researchers in glycobiology, medicinal chemistry, and chemical biology who need stable substrate mimics, enzyme inhibitors, or synthetic intermediates for studying sialylation pathways implicated in infection, immunity, and oncology.
Technical specifications
Key features:
- Two compound classes: triazole-linked dinucleosides and ether-triazole linked dinucleosides, both derived from the CMP-Neu5Ac scaffold
- Replacement of the native phosphodiester linker with a triazole or ether-triazole linkage to enhance chemical and metabolic stability
- Designed to retain sialyltransferase binding activity while improving pharmacokinetic and synthetic properties
- Provides novel nucleoside building blocks suitable for further derivatization and library generation
- Applicable as substrate mimics, enzyme probes, or starting points for inhibitor development in glycosylation research
Technology readiness level
The compounds are at an early research stage, with the design rationale and hypothesis validation described in the proposal. Future validation plans are expected to confirm enzymatic activity, stability improvements, and pharmacokinetic advantages relative to the native CMP-Neu5Ac substrate. The technology is ready for collaborative optimization and further characterization.
About University of Wollongong
The University of Wollongong is a comprehensive public research university in coastal New South Wales with a global outlook and strong applied orientation. Industry engages through the Innovation Campus, a research and technology park that co-locates corporate R&D with university labs, prototyping suites, and pilot-scale facilities. A regional health partnership enables clinical translation and access to patient cohorts, while an on-site incubator and accelerator connects companies with researchers and supports venture creation. Research is backed by competitive national funding, including the Australian Research Council and National Health and Medical Research Council, alongside state and industry support. A dedicated technology transfer office manages IP, licensing, and collaboration agreements with streamlined processes.
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