Preparation of carbohydrate–oligonucleotide conjugates using the squarate spacer

“…A proof of principle for the preparation of carbohydrateoligonucleotide conjugates using the squarate linker has recently been described by Yan and co-workers. 66 With a view to developing glycotargeting constructs, a facile method for the conjugation of lactoside 112, to an amino functionalised dinucleotide was achieved using squaric ester chemistry, progressing through intermediate 113, to provide adduct 114 (Scheme 17). These examples illustrate the utility of the squaramide linker and the compatibility of the squaric ester chemistry with a number of functional groups and aqueous reaction conditions.…”

Section: Bioconjugationmentioning

confidence: 99%

Squaramides: physical properties, synthesis and applications

2011

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Squaramides are remarkable four-membered ring systems derived from squaric acid that are able to form up to four hydrogen bonds. A high affinity for hydrogen bonding is driven through a concomitant increase in aromaticity of the ring. This hydrogen bonding and aromatic switching, in combination with structural rigidity, have been exploited in many of the applications of squaramides. Substituted squaramides can be accessed via modular synthesis under relatively mild or aqueous conditions, making them ideal units for bioconjugation and supramolecular chemistry. In this tutorial review the fundamental electronic and structural properties of squaramides are explored to rationalise the geometry, conformation, reactivity and biological activity.

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“…To attach DNA noncovalently to ConA via sugar binding, a mannose–DNA conjugate was developed using squaramide chemistry (Schemes b and S1). Squaramide linkages have been used extensively to conjugate biomolecules due to their high reaction rate, simple functional group requirements (two primary amines are conjugated together), and the pH dependence of their reactivity, which enables nonsymmetric squaramides to be synthesized by controlling the pH of the conjugation reaction. − The synthesis of sugar–DNA conjugates is presented in detail in the Supporting Information (Scheme S1 and Figures S1–S18). In brief, an amine-functionalized mannose derivative ( Man-6 ) was reacted with methyl squarate ( 7 ) to give a mannose–squaramide conjugate ( Man-8 ).…”

Section: Resultsmentioning

confidence: 99%

Redefining Protein Interfaces within Protein Single Crystals with DNA

et al. 2021

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Proteins are exquisite nanoscale building blocks: molecularly pure, chemically addressable, and inherently selective for their evolved function. The organization of proteins into single crystals with high positional, orientational, and translational order results in materials where the location of every atom can be known. However, controlling the organization of proteins is challenging due to the myriad interactions that define protein interfaces within native single crystals. Recently, we discovered that introducing a single DNA−DNA interaction between protein surfaces leads to changes in the packing of proteins within single crystals and the protein−protein interactions (PPIs) that arise. However, modifying specific PPIs to effect deliberate changes to protein packing is an unmet challenge. In this work, we hypothesized that disrupting and replacing a highly conserved PPI with a DNA−DNA interaction would enable protein packing to be modulated by exploiting the programmability of the introduced oligonucleotides. Using concanavalin A (ConA) as a model protein, we circumvent potentially deleterious mutagenesis and exploit the selective binding of ConA toward mannose to noncovalently attach DNA to the protein surface. We show that DNA association eliminates the major PPI responsible for crystallization of native ConA, thereby allowing subtle changes to DNA design (length, complementarity, and attachment position) to program distinct changes to ConA packing, including the realization of three novel crystal structures and the deliberate expansion of ConA packing along a single crystallographic axis. These findings significantly enhance our understanding of how DNA can supersede native PPIs to program protein packing within ordered materials.

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Preparation of carbohydrate–oligonucleotide conjugates using the squarate spacer

Cited by 8 publications

References 14 publications

Carbohydrate microarrays for screening functional glycans

Carbohydrate microarrays for screening functional glycans

Squaramides: physical properties, synthesis and applications

Redefining Protein Interfaces within Protein Single Crystals with DNA

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