Demystifying a hexuronic acid ligand that recognizes Toxoplasma gondii and blocks its invasion into host cells

Abstract

Toxoplasma gondii is a ubiquitous eukaryotic pathogen responsible for toxoplasmosis in humans and animals.

Profiling Heparan Sulfate‐Heavy Metal Ions Interaction Using Electrochemical Techniques

“…Monosaccharide building blocks 1 – 4 were prepared as reported previously,[ 6 , 25 , 26 ] and were used to synthesize the G tetrasaccharides precursor 7 via a 7 steps procedure (Scheme 1 , and in the Supporting Information). To enable later stage sulfation and derivatization, the O ‐6 hydroxyls of GlcN in 7 were protected with tetrabutyl diphenylsilyl (TBDPS) and O ‐3 hydroxyls were equipped with naphthylmethyl (Nap).…”

Sulfation of Heparan and Chondroitin Sulfate Ligands Enables Cell‐Specific Homing of Nanoprobes

“…Next, we synthesized galactosamine donor 20 and glucose acceptor 17 from d ‐galactosamine and d ‐glucose in 6 and 7 steps, respectively, as reported in the literature [23b,24] . The glucose donor 19 was further modified with 6‐ O ‐chloroacetate protection, followed by linker glycosylation that yielded acceptor 19 in 68 % yield.…”

Sulfation Code and Conformational Plasticity of l-Iduronic Acid Homo-Oligosaccharides Mimic the Biological Functions of Heparan Sulfate

“…The nearly 100 years of progress in heparan sulfate/heparin (HS/HP) research has led to numerous advances in the development of anticoagulants and in cancer theranostics. − Nonetheless, complete utilization of HS/HP in clinical settings remains elusive due to the structural heterogeneity and the inability to synthesize all possible HS oligosaccharides. − For example, despite the emergence of efficient chemical and enzymatic methods to synthesize HS oligosaccharides, only a small number of synthetic HS analogs have been reported. − These challenges are further exacerbated by the limited ability to structurally characterize them and track their biological functions . The recognition of HS by the myriad of protein surfaces , is modulated by its four key inherent structural aspects, (a) sulfation patterns ( O - and N -sulfation), − (b) uronic acid composition ( l -iduronic acid (IdoA) and d -glucuronic acid), (c) oligosaccharide chain length, ,, and (d) conformation plasticity of IdoA. − These four factors dictate the ability of a specific HS domain to bind proteins, challenging the discovery of specific HS structural domains to modulate individual heparan sulfate binding protein (HSBP) activity. This challenge has spurred the development of biomimetic analogs of HS and their study in molecular recognition processes.…”

“…7−9 These challenges are further exacerbated by the limited ability to structurally characterize them and track their biological functions. 10 The recognition of HS by the myriad of protein surfaces 11,12 is modulated by its four key inherent structural aspects, (a) sulfation patterns (O-and N-sulfation), 13−15 (b) uronic acid composition (L-iduronic acid (IdoA) and Dglucuronic acid), 16 (c) oligosaccharide chain length, 11,12,17 and (d) conformation plasticity of IdoA. 18−22 These four factors dictate the ability of a specific HS domain to bind proteins, challenging the discovery of specific HS structural domains to modulate individual heparan sulfate binding protein (HSBP) activity.…”