Anti-NCL monoclonal antibody, clone FQS8063

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. The social amoeba Dictyostelium discoideum has proven to be an exceptional model organism for studying a wide range of neurological disorders, including the NCLs. The Dictyostelium genome contains homologs of 11 of the 13 NCL genes. Its life cycle, comprised of both single-cell and multicellular phases, provides an excellent system for studying the effects of NCL gene deficiency on conserved cellular and developmental processes. In this review, we highlight recent advances in NCL research using Dictyostelium as a biomedical model.

Cysteine-based native chemical ligation (NCL) has been a very powerful approach for convergent synthesis of peptides and proteins. However, owing to the low abundance of cysteine (Cys) in proteins, applications of NCL in protein chemical synthesis are limited. To expand the peptide ligation toolbox, NCL followed by desulfurization has been developed to enable peptide ligation at Xaa-Ala conjunctions, that is, formal "alanine ligation". In this regard, effective peptide desulfurization methods are critical. This Concept article summarizes the development of different desulfurization strategies for peptide and protein chemical synthesis.