Abstract
The synthesis of robust oligomers of sialic acid (ROSAs), composed of α-(17)-linked acylhydrazine oligosaccharides, to be used in the future preparation of sulfoglycodendrimers (SGDs) as antiviral agents targeting HIV and SARS-CoV-2, is reported here. The speed and ferocity at which the SARS-CoV-2 pandemic spread emphasizes the need for broad spectrum antiviral agents which can serve to inhibit the spread of established and emerging viruses. Despite the relatively quick rollout of multiple vaccines against SARS-CoV-2, there exists the need for multiple means by which to slow or stop the spread of the virus, evident in the continuing infections that have occurred despite vaccine development and deployment. It is now well established that host cell heparan-sulfate proteoglycans (HSPGs) are necessary to the binding step of numerous viral life cycles. Viral dependence on these HSPGs is exploited here, and the goal is to create molecular mimics which bind to both the HIV gp120 and SARS-CoV-2 spike proteins, thereby inhibiting the viruses’ ability to bind to host receptors. Synthesis of the proposed ROSA structures involves the synthesis of two sialic acid derivatives, a glycosyl acceptor and a glycosyl donor formed using a single sialic acid derivative as their precursor. The stability of the ROSA inter-residue acylhydrazine linkages is greater than that of the native α-(18)-glycosidic linkage of colominic acid, which has shown to have anti-HIV properties in the sulfated form. The ROSAs produced here were characterized using 1H-NMR, 13C-NMR, COSY, and HSQC. Finally, glycosyl donor used to generate the oligomers will show its utility through the conjugation to a commercially available carboxy-terminated PAMAM dendrimer through the acylhydrazine, yielding an N,N’-diacylhydrazine linked glycodendrimer.