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AqueaTether® (AqT®) Technologies

CellMosaic is developing next-generation bioconjugation kits and products based on its proprietary super-hydrophilic and high-loading AqT linkers. AqT linkers are innovative, proprietary biomaterials developed at CellMosaic, featuring novel chemical architectures derived from a class of natural and edible sugar alcohol compounds. AqT molecules are specifically for labeling and conjugating biomolecules with highly hydrophobic small molecules, such as fluorescent compounds, biotin, and small-molecule drugs. Branched AqT^® crosslinking reagents can also be customized to load a high amounts of detecting molecules onto a biomolecule for enhanced detection.

The AqT platform can also be applied to create new and improved therapeutics across a broad range of drug molecules and treatment indications. This platform can significantly accelerate the drug discovery by delivering optimized entities for development. It offers a versatile approach to developing new chemical entities (NCE) or new biological entities (NBE) with optimized drug profiles. The AqT platform provides a simple solution to complex issues such as bioavailability, stability, and toxicity faced by many hydrophobic small-molecule drugs and large-molecule biologics. For more information on AqT technologies in drug development, please visit our website at www.aqttherapeutics.com

Structure of AqT® Linkers

Sugar molecules are among the most hydrophilic natural compounds due to their hydrogen bonding capability (both donor and acceptor). Sugar alcohol, also known as polyol, is a hydrogenated form of carbohydrate in which the carbonyl group (aldehyde or ketone) has been reduced to a primary or secondary hydroxyl (OH) group. Sugar alcohols occur naturally in foods and are derived from plant products, such as fruits and berries. They are often used as ingredients in sweeteners and for producing polymers like hydrogel. 

CellMosaic has developed advanced methods to assemble highly sophisticated AqT® architectures from sugar alcohol monomers. Additionally, methods have been established to convert the OH groups of sugar alcohol into other crosslinking groups, such as aminooxy, maleimide, halide, azide, cyclooctyne, ketone, thioester, and N-hydroxysuccinimide ester (NHS). Table 1 lists some popular sugar alcohols used in the creation of AqT linkers.

3- Carbon	4- Carbon	5-Carbon	6-Carbon
Glycerol	Erythritol	Arabitol	Mannitol
	Threitol	Xylitol	Sorbitol
		Ribitol	Galactitol
			Fucitol
			Iditol

 Table 1: Sugar alcohols that can be used for making AqT™ crosslinkers.

Advantages of AqT^® Linkers

The advantages of AqT linkers over traditional linkers and polydisperse carrier polymers are numerous:

1) Super-hydrophilicity:  AqT linkers are among the most hydrophilic molecules in development, offering the ability to modulate molecular properties after conjugation.

Figure 1. C18 HPLC analysis of AqT linker and other commercial linkers.

2) Versatility in crosslinking: AqT linkers allow for the creation of crosslinking reagents with a wide range of functional groups, making them the most versatile and tunable molecules currently in development.

Figure 2. C18 column HPLC analysis of mono-dispersed AqT molecules of various SA units.

3) Enhanced water solubility: AqT crosslinker can significantly increase the water solubility of hydrophobic compounds, enabling conjugation to be performed in aqueous buffer

Figure 3. C18 HPLC analysis of a hydrophobic drug before and after di-SA unit AqT-linker labeling

4) Biocompatible: The biopolymer's Properties remain unchanged after AqT mediated labeling and conjugation with small molecules

Biopolymers, such as antibodies and proteins/peptides, labeled with hydrophobic small molecules tend to aggregate and precipitate out of solution over time. AqT linker are designed to modify these small molecules, enhancing their hydrophilicity and water solubility. The hydroxy (-OH) groups of AqT create a network of hydrogen bonds (H-bond) with surrounding water molecules, forming a microenvironment that shields neighboring small molecules or crosslinking moieties from stacking or interacting with each other. As a result, biopolymers can be labeled with a high amount of AqT-small molecules without altering their inherent properties. This AqT-enhanced H-bond network also protects polymers from enzymatic degradation, helping them retain its activities.

Examples: Antibody biotinylation using AqT T2A15 linker (see HPLC data in Figures 4, 5, and 6). 

The AqT T2A15 linker consists of two threitols and spans 15 atoms in length, comparable to four polyethylene glycol-modified biotin (PEG4, 16 atom lengths). However, unlike PEG4, AqT™ significantly increases the hydrophilicity of biotin. 

Patent and License Restrictions 

AqT™ molecules are covered under WO2013/012961A2, US patent numbers 8907079B2, 9511150B2, US15/281,023, Chinese patent 201280034231.3, Australian patent 2012284055, Japan patent 2014-521744, and equivalent patents and patent applications in other countries, all in the name of CellMosaic, Inc. We are currently marketing limited AqT™ products for internal research and development. 

The purchase of AqT products includes a limited license to use them for internal research and development purpose only, and not for any commercial purposes. Commercial use includes, but is not limited to:

1. The sale, lease, license or other transfer of the material or any material derived or produced from it.

2. The sale, lease, license or other grant of rights to use this material or any material derived or produced from it.

3. The use of this material to perform services for a fee for third parties, including contract research and drug screening.

If you are interested in using AqT for commercial purposes, please contact us for more information. For partnering and collaboration in the development of AqT therapeutics, visit our website at www.aqttherapeutics.com for more details.