In this section
@article{Youn:2025:10.1021/acs.bioconjchem.4c00556,
author = {Youn, T and Kim, G and Hariharan, P and Li, X and Ahmed, W and Byrne, B and Liu, X and Guan, L and Chae, PS},
doi = {10.1021/acs.bioconjchem.4c00556},
journal = {Bioconjug Chem},
title = {Improved Pendant-Bearing Glucose-Neopentyl Glycols for Membrane Protein Stability.},
url = {http://dx.doi.org/10.1021/acs.bioconjchem.4c00556},
year = {2025}
}
TY - JOUR
AB - Membrane proteins are biologically and pharmaceutically significant, and determining their 3D structures requires a membrane-mimetic system to maintain protein stability. Detergent micelles are widely used as membrane mimetics; however, their dynamic structures often lead to the denaturation and aggregation of encapsulated membrane proteins. To address the limitations of classical detergents in stabilizing membrane proteins, we previously reported a class of glucose-neopentyl glycols (GNGs) and their pendant-bearing versions (P-GNGs), several of which proved more effective than DDM in stabilizing membrane proteins. In this study, we synthesized additional GNG derivatives by varying the lengths of the pendant (P-GNGs), and by introducing hemifluorinated pendants to the GNG scaffold (fluorinated pendant-bearing GNGs or FP-GNGs). The synthetic flexibility of the GNG chemical architecture allowed us to create a diverse range of derivatives, essential for the effective optimization of detergent properties. When tested with two model membrane proteins (a transporter and a G-protein coupled receptor (GPCR)), most of the new (F)P-GNGs demonstrated superior stabilization of these membrane proteins compared to DDM, the original GNG (OGNG)), and a previously developed P-GNG (i.e., GNG-3,14). Notably, several P-GNGs synthesized in this study were as effective as or even better than lauryl maltose neopentyl glycol (LMNG) in stabilizing a human GPCR, beta2 adrenergic receptor (β2AR). Enhanced protein stability was particularly observed for the P-GNGs with a butyl (C4) or pentyl (C5) pendant, indicating that these pendant sizes are optimal for membrane protein stability. The volumes of these pendants appear to minimize the empty spaces in the micelle interiors, thereby enhancing detergent-detergent interactions in micelles complexed with the membrane proteins. Additionally, we identified one FP-GNG that was more efficient at extracting the transporter and more effective at st
AU - Youn,T
AU - Kim,G
AU - Hariharan,P
AU - Li,X
AU - Ahmed,W
AU - Byrne,B
AU - Liu,X
AU - Guan,L
AU - Chae,PS
DO - 10.1021/acs.bioconjchem.4c00556
PY - 2025///
TI - Improved Pendant-Bearing Glucose-Neopentyl Glycols for Membrane Protein Stability.
T2 - Bioconjug Chem
UR - http://dx.doi.org/10.1021/acs.bioconjchem.4c00556
UR - https://www.ncbi.nlm.nih.gov/pubmed/40105011
ER -
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