RESUMO
Neoglycoconjugates mimicking natural compounds and possessing a variety of biological functions are very successful tools for researchers to understand the general mechanisms of many biological processes in living organisms. These substances are characterized by high biotolerance and specificity, with low toxicity. Due to the difficult isolation of individual glycoclusters from biological objects, special interest has been directed toward synthetic analogs. This review is mainly focused on the one-pot, double-click methodology (containing alkyne-azide click cycloaddition with the following 6π-azaelectrocyclization reactions) used in the synthesis of N-glycoconjugates. Homogeneous (including one type of biantennary N-glycan fragments) and heterogeneous (containing two to four types of biantennary N-glycan fragments) glycoclusters on albumin were synthesized via this strategy. A series of cell-, tissue- and animal-based experiments proved glycoclusters to be a very promising class of targeted delivery systems. Depending on the oligosaccharide units combined in the cluster, their amount, and arrangement relative to one another, conjugates can recognize various cells, including cancer cells, with high selectivity. These results open new perspectives for affected tissue visualization and treatment.
Assuntos
Glicoconjugados/síntese química , Polissacarídeos/química , Albumina Sérica Humana/química , Animais , Catálise , Técnicas de Química Sintética , Química Click , Glicoconjugados/química , Humanos , Lectinas/química , Camundongos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The concept of "therapeutic in vivo synthetic chemistry" refers to chemical synthesis in living systems using new-to-nature reactions for the treatment or diagnosis of diseases. This review summarizes our development of therapeutic in vivo synthetic chemistry using glycan-modified human serum albumin (glycoHSA) and utilizing the selective glycan-targeting and metal protective effects of metal catalysts. The four artificial metalloenzymes with glycoHSA provided good cancer treatment results based on on-site drug synthesis and selective cell-tagging strategies. Thus, we propose that therapeutic in vivo synthetic chemistry using glycoHSA as a new modality of therapy or diagnosis is applicable to a wide range of diseases.