Combinatorial synthesis of a hyaluronan based polysaccharide library for enhanced CD44 binding

Chemical modification of hyaluronan oligosaccharides differentially modulates hyaluronan- hyaladherin interactions

“…Thus, the aromatic rings of the aminobenzoic acid moieties studied here could be involved in similar stacking interactions within this pocket, resulting in the improved affinities observed (see Figure 1). Our data are also consistent with recent work (48) demonstrating that polymeric HA (10 kDa) modified with multiple aromatic amines generated the best inhibitor of binding of unmodified HA to CD44 (although direct comparison of these IC50 values with the KD values from our study is not possible). The (modest) gain in affinity achieved with modified HA4 AN , reported here, supports the strategy of using HA oligosaccharide as scaffolds to enhance the binding to target HABPs.…”

“…Therefore, they represent a good starting point, especially since short HA oligomers provide ready-made scaffolds for chemical modification (47). Lu and Huang (48) used HA tetrasaccharides as scaffolds to generate compounds that could potentially inhibit binding of HA to CD44 in competition assays. In addition to single modifications to oligosaccharides, chemical derivatization of polymeric HA ( e.g., 10 kDa and above) has also been described as a strategy to generate inhibitors or probes for HABPs.…”

“…In addition to single modifications to oligosaccharides, chemical derivatization of polymeric HA (e.g., 10 kDa and above) has also been described as a strategy to generate inhibitors or probes for HABPs. Liu et al (48) recently reported the generation of a library of carboxyl-modified HA polysaccharides containing two derivatives that could inhibit binding of native HA to CD44; the inhibitory potential of these derivatives increased with the size of the HA modified, likely due to the multivalency and superselectivity of CD44-HA binding (10,11,(48)(49)(50). However, some modifications to polymeric HA reduce binding affinity, for example sulfation of the 6O-groups of GlcNAc prevents binding of the modified HA to CD44 (51,52).…”

Robust Synthesis of Targeting Glyco‐Nanoparticles for Surface Enhanced Resonance Raman Based Image‐Guided Tumor Surgery

“…Breast cancer cell 4T1 was explored as the target cell, which expresses a high level of CD44 on the surface. [63,64] 4T1 cells were incubated with solutions of liposome-SERS-PEG and liposome-SERS-HA respectively under the same experimental conditions. The cells were then rinsed with the buffer to remove the unbound particles, and Raman signals were recorded.…”

Combinatorial discovery of antibacterials via a feature-fusion based machine learning workflow

“…However, combinatorial libraries for target screening are typically limited in size ranging from tens to hundreds of compounds and tend to follow the pre-existing molecular scaffolds to raise the hit rate. 18,19 The attempt to exponentially expand the potential chemical space necessitates highthroughput pipelines to manage the huge pool of candidates such as DNA-encoded libraries 15,20 and micro-dispensers, 21 which has arisen concerns regarding cost efficiency. Furthermore, the process of analyzing the collected data and extracting meaningful insights remains a laborious task.…”