Glycosaminoglycans (GAGs) as one major part of the glycocalyx are involved in many essential biological cell processes, as well as in many courses of diseases. Because of the potential therapeutic application of GAG polymers, fragments, and also derivatives toward different diseases (e.g., heparin derivatives against Alzheimer's disease), there is a continual growing demand for new chemical syntheses, which suffice the high claim to stereoselectivity and chemoselectivity. This Review summarizes the progress of chemical syntheses of GAGs over the last 10 years. For each class of the glycosaminoglycans-hyaluronan (HA), heparan sulfate/heparin (HS/HP), chondroitin/dermatan sulfate (CS/DS), and keratan sulfate (KS)-mainly novel glycosylation strategies, elongation sequences, and protecting group patterns are discussed, but also (semi)automated syntheses, enzymatic approaches, and functionalizations of synthesized or isolated GAGs are considered.

Single glycan-protein interactions are often weak, such that glycan binding partnerscommonly utilizemultiple, spatially defined binding sites to enhance binding avidity and specificity.C urrent array technologiesu sually neglect defined multivalent display.L aser-based array synthesis technology allows for flexible and rapid on-surface synthesis of different peptides. By combining this technique with click chemistry,n eo-glycopeptides werep roduced directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well-defined glycan structures for multivalent display.T he two lectins concanavalin Aa nd langerin were probedw ith different glycanso nm ultivalent scaffolds, revealing strong spacing-, density-, and ligand-dependent binding. In addition, we could also measuret he surfaced issociation constant.T his approach allows for ar apid generation, screening, and optimization of am ultitudeo fm ultivalent scaffoldsfor glycan binding.

In this introductory lecture we discuss the state-of-the-art glycan microarray technology, with emphasis on novel approaches to immobilize collections of glycans in a defined, multivalent manner.

A low‐cost laser‐based printing setup is presented, which allows for the spot‐wise patterning of surfaces with defined polymer nanolayers. These nanolayer spots serve as a “solid solvent,” embedding different chemicals, chemical building blocks, materials, or precursors and can be stacked on top of each other. By melting the spot pattern, the polymer‐embedded molecules are released for chemical reaction. This enables researchers to quickly pattern a surface with different molecules and materials, mixing them directly on the surface for high‐throughput chemical synthesis to generate and screen diverse microarray libraries. In contrast to expensive ink‐jet or contact printing, this approach does not require premixing of inks, which enables in situ combinatorial mixing. Easy access and versatility of this patterning approach are shown by generating microarrays of various biomolecules, such as glycans for the first time, to screen interactions of antibodies and lectins. In addition, a layer‐by‐layer solid‐phase synthesis of peptides directly on the microarray is presented. Amino acid–containing nanolayers are repeatedly laser‐transferred and reacted with the functionalized acceptor surface in defined patterns. This simple system enables a reproducible array production, down to spot‐to‐spot distances of 100 µm, and offers a flexible and cheap alternative to expensive spotting robot technology.

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