Triblock peptide-linker-lipid molecular design improves potency of peptide ligands targeting family B G protein-coupled receptors.
Two peptide-linker-lipid constructs were designed and prepared which target the parathyroid hormone 1 receptor, a family B G protein-coupled receptor. Both show increased agonist activity in a cell-based assay. The lipid moiety enables the formation of micelle-like nanostructures, which is shown to hinder proteolytic digestion and is expected to reduce renal clearance.
Department of Chemistry, Yale University, New Haven, CT 06520, USA. elsa.yan@yale.edu.
Yuting
Y
Liu
Yingying
Y
Cai
Wei
W
Liu
Xiao-Han
XH
Li
Elizabeth
E
Rhoades
Elsa C Y
EC
Yan
D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D013329:Structure-Activity Relationship
D008024:Ligands; D008055:Lipids; C473449:PTH1R protein, human; D010455:Peptides; D044168:Receptor, Parathyroid Hormone, Type 1