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Technologies for Directed Evolution of Glycoaptamers

糖适体定向进化技术

基本信息

批准号：
10721663
负责人：
Isaac Jonathan Krauss
金额：
$ 42.12万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10721663
关键词：
Acceleration Acids Affinity Allergens Atherosclerosis Autoimmunity Avidity Bar Codes Binding Binding Sites Biological Biological Process C-Type Lectins CD209 gene Carbohydrates Categories Cell Adhesion Chemicals Communicable Diseases Complex DNA Defense Mechanisms Diabetes Mellitus Diagnostic Directed Molecular Evolution Disease Elements Evolution Exhibits Eye Fibrosis Galactose Galactose Binding Lectin Galectin 1 Generations Geometry Glycobiology Goals HIV Antibodies HIV vaccine Hand Heart Immunity Immunosuppression Individual Internet Interruption Lectin Libraries Ligand Binding Ligands Link Liver Lung Macrophage Malignant Neoplasms Mannose Medicine Methods Modification Names Nucleic Acids Pharmaceutical Chemistry Pharmaceutical Preparations Polymers Polysaccharides Process Property Protein-Carbohydrate Interaction Proteins RNA Research Resistance Rheumatoid Arthritis Role Serum Sialic Acids Signal Transduction Specificity Technology Testing Validation Variant Vertebral column Viral Virus Diseases Work angiogenesis aptamer carbohydrate binding protein carbohydrate receptor chelation desensitization design flexibility glycosylation immunoregulation in vivo inhibitor interest langerin member non-drug nuclease pathogen protein function rapid technique response scaffold sialic acid binding Ig-like lectin small molecule sugar therapeutic development tool

项目摘要

Project Summary/Abstract The goal of this Focused Technology R01 project is to develop technologies for rapid discovery of inhibitors of carbohydrate-binding proteins (CBPs). Carbohydrate-protein interactions are critical in numerous processes including host-pathogen recognition, cell adhesion and cell signaling, cancer angiogenesis, immune suppression, heart/liver/lung/eye fibrosis, atherosclerosis, diabetes, and rheumatoid arthritis, to name a few examples. However, selective disruption of specific CBP interactions is challenging in vivo. CBPs generally bind weakly to individual glycans, with higher affinity (avidity) or specificity coming from multivalent interactions to clustered glycans or interactions with nearby non-carbohydrate elements. A given CBP also usually binds to various glycans. To untangle the complex web of CBP functions, it is important to have a way to rapidly develop a specific and potent inhibitor of a CBP that can be used in the relevant in vivo context. To this end, we propose two Aims: 1) to develop multivalent glyco-F-RNA aptamers, in which a nuclease-resistant, F-RNA backbone is evolved to present simple glycans in a manner that is selectively recognized by a CBP of interest; 2) to develop monovalent glyco- F-RNA aptamers, in which a simple glycan provides a binding “foothold” for the CBP of interest, which the evolved F-RNA component confers additional binding affinity and specificity through interactions auxiliary to the glycan-binding pocket.

项目总结/文摘