Rationally designed small molecules to prevent type 1 diabetes.

ABSTRACT: PURPOSE OF REVIEW:To review the recent findings that small 'drug-like' compounds block disease-specific human leukocyte antigen (HLA) molecules in type 1 diabetes (T1D). RECENT FINDINGS:The predominant genetic risk for developing T1D, the immune-mediated form of diabetes, is conferred through HLA genes. One such gene, termed HLA-DQ8, is present in 50-60% of patients with T1D and those at-risk. DQ8 presents disease-relevant peptides to T cells, which mediate tissue-specific destruction of pancreatic islets. Using a structure-based approach to evaluate the 'druggability' of the DQ8 molecule, methyldopa, a clinically well-established oral antihypertensive agent, was discovered to bind DQ8. Methyldopa blocked the activation of DQ8-specific T cells responding to self-antigens such as insulin bu

SUBMITTER: Ostrov DA 

PROVIDER: S-EPMC6764771 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature