Lectin Drug Conjugates Targeting High Mannose N‐Glycans

Abstract

Cancer-associated alterations to glycosylation have been shown to aid cancer development and progression. An increased abundance of high mannose N-glycans has been observed in several cancers. Here, we describe the preparation of lectin drug conjugates (LDCs) that permit toxin delivery to cancer cells presenting high mannose N-glycans. Additionally, we demon-strate that cancer cells presenting low levels of high mannose N-glycans can be rendered sensitive to the LDCs by cotreatment with a type I mannosidase inhibitor. Our findings establish that an increased abundance of high mannose Nglycans in the glycocalyx of cancer cells can be leveraged to enable toxin delivery.

Lectin‐anticancer peptide fusion demonstrates a significant cancer‐cell‐selective cytotoxic effect and inspires the production of “clickable” anticancer peptide in Escherichia coli

“…The biorthogonal click reaction was specific to the azide in rRDP215 20AzK but did not occur with the synthetic peptide RDP215, which we used as the control. The cytotoxicity of recombinant rRDP215 and the cancer cell binding ability of recombinant rRDP215‐Cy3 evidently qualifies the molecule for bioconjugations, for example, with tumor‐targeting antibody fragments (Cortez‐Retamozo et al, 2002 ), lectins (Kurhade et al, 2022 ), nanoparticles (Vaughan et al, 2020 ) and small molecules (Liu et al, 2022 ) to generate new tools for cancer‐cell‐selective therapy and imaging of cancer cells or cancer metastasis.…”

Preparation of Dual‐activity Enzyme‐metal‐nanoparticles Conjugate Catalysts for Cascade Processes

“…The potential of these bifunctional nanobiohybrids has recently been applied in the consecutive and parallel synthesis of glycoderivatives, [31,34] which are very important intermediates in the synthesis of various drugs and vaccines, but also in the fabrication of early diagnosis and more effective and targeted therapeutic tools. [45][46] The solid-phase enzyme-metal nanoparticles dual catalysts were successfully applied in both cases. This technique enables the production of completely active enzyme and metal active sites that are intramolecularly positioned at a position where a very efficient reaction can take place.…”

Solid‐Phase Lipase‐CuNPs Biohybrids as Catalysts for One‐Pot Parallel Synthesis of 2,3,4‐Triacetyl‐D‐Gluconic Acid

“…Glycans derivatives are extremely important molecules in key biological processes. They are involved in regio‐ and stereochemical controlled fabrication of glycosylated molecules, as drug and vaccines, but also in fabrication of early diagnosis and more effective and targeted therapeutic tools [1–5] . In this respect, one of the most difficult entities is the fabrication of partially protected sugars (monosaccharides) with orthogonal functional groups as key intermediates, which required extremely time‐consuming processes with multiple steps and specific purification steps, finally resulting in moderate or low yields of target product at the end [6]…”

“…They are involved in regio-and stereochemical controlled fabrication of glycosylated molecules, as drug and vaccines, but also in fabrication of early diagnosis and more effective and targeted therapeutic tools. [1][2][3][4][5] In this respect, one of the most difficult entities is the fabrication of partially protected sugars (monosaccharides) with orthogonal functional groups as key intermediates, which required extremely timeconsuming processes with multiple steps and specific purification steps, finally resulting in moderate or low yields of target product at the end. [6] In particular, gluconic acid and its derivatives have been applied globally with different shares in the construction (45 %), food (35 %), medicine (10 %) and other (10 %) industries.…”