Heparin-based Mimetic Development Service

Marine carbohydrates contain a variety of gluconic acids and sulfate groups and are valuable resources for the development of heparin drugs. Heparin is the most successful anticoagulant agent and plays a key role in various biological processes. Heparin interferes with the signaling pathway of advanced glycation end-products (RAGE) ligands in disease by interacting with RAGE. CD BioGlyco achieves the purpose of regulating the biological activity of living organisms by rationally designing heparin-based mimetics and changing their structural properties including chain length, stereochemistry, and sulfation patterns.

Heparin-based Mimetic Development Service at CD BioGlyco

CD BioGlyco provides clients with heparin-based mimetic preparation services based on the condition that Carbohydrate Mimetics have adjustable multivalent interactions with proteins and other biological targets. Furthermore, specific characterization of heparin-based mimetic structures helps clients explore bioactive mimetics for multiple biological applications.

Novel Chemoenzymatic Synthesis

We have a comprehensive chemoenzymatic synthesis strategy for the rapid and accurate assembly of novel heparin-based mimetics. Our investigators continuously optimize key factors in the synthetic process, including better enzyme expression, improved biocatalyst using protein engineering and fixation, high-quality production of enzyme cofactors, optimization of enzyme conversion, and development of efficient technologies such as the use of ultraviolet (UV) absorption or fluorescence tags, detection and purification of synthetic intermediates.

Meanwhile, we offer several synthesis services including one-pot reactions, Smith and alkaline degradation, and solid-phase synthesis. We have corresponding synthesis routes to provide based on the design of different mimetics. All your molecular synthesis and design requirements always communicate with technicians and we will give you a satisfactory solution.

Functional Characterization

For the synthetic target mimics, we use nuclear magnetic resonance (NMR), mass spectrometry (MS), ion chromatography, surface plasmon resonance (SPR), and zeta potential analysis to provide detection and evaluation services.

Fig.1 Flow chart of heparin-based mimetic development services. (CD BioGlyco)

Publication

Technology: NMR, SPR

Journal: ACS Macro Letters

IF: 6.131

Published: 2019

Results: Six heparin-based mimetics are efficiently synthesized by a combination of chemoenzymatic methods. The synthesis mainly involved enzymatic extension and chemical sulfation modifications. In this study the chemical sulfation modification reaction was accomplished using microblog irradiation, and the results showed that regioselective 6-O-sulfation and overall desulfation carried out a good modification. The success of the sulfation was indicated by the position forward analysis of the signal on the sugar ring in the NMR spectrum. Testing the binding of heparin-based mimetics to RAGE by SPR revealed that the non-sulfated heparin-based mimetics were essentially unbound to RAGE, and the all-O-sulfated heparin-based mimetics showed high binding capacity. In particular, the overall trisaccharide sulfate-modified hs mimetic glycoconjugates showed the highest affinity.

Fig.2 NMR spectra of four different heparin-based mimetics. (Li, et al., 2019)

Applications of Heparin-based Mimetic

• Heparin-based mimetics promotes RAGE oligomerization and activates the signaling pathways of RAGE ligands. Reducing RAGE ligand signaling by targeting heparin-based mimetic-RAGE interaction with potent antagonists aims to improve disease development.
• In addition to small molecule antagonists, heparin-based mimetics also act as potential antagonists of RAGE through competitive binding. Especially with the O-sulfate sugar group modification heparin-based mimetic.
• Heparin-based mimetics are used clinically for the treatment of deep vein thrombosis, reducing the risk of side effects.
• Heparin-based mimetics effectively inhibit the interaction of the SARS-CoV-2 spike glycoprotein (SGP) with the cell surface angiotensin-converting enzyme 2 (ACE 2) receptor. Thus, heparin-based mimetic as an innovative viral nasal spray, is being explored as an adjunctive therapy in the treatment of SARS-CoV-2.
• Heparin-based mimetics act as a broad-spectrum inhibitor of different viruses to provide the basis for developing novel antiviral agents.

Advantages of Us

• Our company provides the multigram grade synthesis service of low molecular weight heparin-based mimetics, and the mimics have good anticoagulant activity.
• Our development team helps clients fully overcome the side effects of repeated steps based on protection, activation, coupling, and deprotection.
• We provide chemoenzyme synthesis services with higher yield, higher purity, easy purification, larger scale, and more structurally complex targets.

CD BioGlyco is a glycobiology company to provides various Marine Biomolecule production and analysis. Moreover, we provide professional marine carbohydrate-based Biomaterial Engineering and Related Biomarker development services. If you are interested in marine carbohydrate mimetic, please feel free to contact us.