Click and Pick: Identification of Sialoside Analogues for Siglec‐Based Cell Targeting

Rillahan, Cory D.; Schwartz, Eduard; McBride, Ryan; Fokin, Valery V.; Paulson, James C.

doi:10.1002/anie.201205831

Cited by 86 publications

(134 citation statements)

References 25 publications

(29 reference statements)

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…D24 bound Siglec-9 on Chinese hamster ovary cells, even in the presence of cis ligands, and was not recognized by other Siglecs [67,82]. Siglec-9-targeted liposomes were generated by covalently binding D24 to PEGylated lipids and implanting the complexes into liposomal nanoparticles.…”

Section: Natural Ligands For Siglec-9 and Siglec-ementioning

confidence: 99%

“…Siglec-9-targeted liposomes were generated by covalently binding D24 to PEGylated lipids and implanting the complexes into liposomal nanoparticles. Siglec-9-expressing Chinese hamster ovary cells interacted with and proceeded to endocytose these particles [82]. Siglec-9-expressing leukocytes can also be targeted by D24-liposome complexes, with an affinity proportional to the concentration of Siglec-9.…”

Section: Natural Ligands For Siglec-9 and Siglec-ementioning

confidence: 99%

See 1 more Smart Citation

Targeting Neutrophils in Severe Asthma via Siglec-9

Chen

Bai

Han

et al. 2018

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Severe asthma comprises only 5% of patients with asthma, but the burden it brings to the social health system accounts for more than half of all asthmatics. Clinical evidence shows that severe asthma is often linked to the recruitment and activation of neutrophils in the airways. However, the underlying molecular and immunological mechanisms of neutrophilia in severe asthma are not clear and currently available drugs exert only limited effects on neutrophilic inflammation. Great efforts are underway to address the mystery of neutrophilic inflammation in chronic respiratory disorders. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are members of the immunoglobulin gene family. Of note, Siglec-9 is uniquely expressed by human neutrophils and monocytes, as well as a minor population of natural killer cells. Engaging this structure with antibodies or glycan ligands results in programmed cell death in human neutrophils. Intriguingly, the administration of Siglec-E antibody abolished the recruitment of neutrophils in mouse models of neutrophilic pulmonary inflammation in vivo. Given that neutrophils are probably a major culprit in the generation and perpetuation of inflammation, targeting Siglec-9 could be beneficial for the treatment of severe asthma, chronic obstructive pulmonary disease, and related pulmonary disorders characteristic of neutrophilia.

show abstract

Section: Natural Ligands For Siglec-9 and Siglec-ementioning

confidence: 99%

Section: Natural Ligands For Siglec-9 and Siglec-ementioning

confidence: 99%

Targeting Neutrophils in Severe Asthma via Siglec-9

Chen

Bai

Han

et al. 2018

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…The most successful approach to date has been to use sialic acid as a privileged scaffold, with modifications made around the sugar ring, primarily at C9 and C5, to increase affinity and selectivity for the desired siglec. 31–41 …”

Section: Introductionmentioning

confidence: 99%

Disubstituted sialic acid ligands targeting siglecs CD33 and CD22 associated with myeloid leukaemias and B cell lymphomas

et al. 2014

Self Cite

View full text Add to dashboard Cite

The siglec family of sialic acid-binding proteins are endocytic immune cell receptors that are recognized as potential targets for cell directed therapies. CD33 and CD22 are prototypical members and are validated candidates for targeting acute myeloid leukaemia and non-Hodgkin’s lymphomas due to their restricted expression on myeloid cells and B-cells, respectively. While nanoparticles decorated with high affinity siglec ligands represent an attractive platform for delivery of therapeutic agents to these cells, a lack of ligands with suitable affinity and/or selectivity has hampered progress. Herein we describe selective ligands for both of these siglecs, which when displayed on liposomal nanoparticles, can efficiently target the cells expressing them in peripheral human blood. Key to their identification was the development of a facile method for chemo-enzymatic synthesis of disubstituted sialic acid analogues, combined with iterative rounds of synthesis and rapid functional analysis using glycan microarrays.

show abstract

“…Finally, the on-chip synthesis of inhibitor libraries is an attractive strategy for the future rapid creation of potent and selective lectin antagonists or enzyme inhibitors in a highly parallel fashion, taking privileged glycan structures as starting scaffolds [93][94][95]. First examples in this direction are the enzymatic on-chip diversification of glycan scaffolds in nano-droplets [17], or the on-chip synthesis of potential Siglec antagonists employing click reactions for the introduction of a second library of structural substituents [49].…”

Section: Detection Of Serum Anti-carbohydrate Antibodies Anticancer Vmentioning

confidence: 99%