@article {D0DT00845A,
	title = {tBu4octapa-alkyl-NHS for Metalloradiopeptide Preparation},
	journal = {Dalton Trans.},
	volume = {49},
	year = {2020},
	month = {05/2020},
	pages = {7605 - 7619},
	publisher = {The Royal Society of Chemistry},
	abstract = {<p>The peptide is an important class of biological targeting molecule; herein{,} a new bifunctional octadentate non-macrocyclic H4octapa{,} tBu4octapa-alkyl-NHS{,} which is compatible with solid-phase peptide synthesis and thus useful for radiopeptide preparation{,} has been synthesized. To preserve denticity{,} the alkyl-N-hydroxylsuccinimide linker was covalently attached to the methylene-carbon on one of the acetate arms{,} yielding a chiral carbon center. According to density-functional theory (DFT) calculations using [Lu(octapa-alkyl-benzyl-ester)]- as a simulation model{,} the chirality has minimal effects on the complex geometry; regardless of the S-/R-stereochemistry{,} DFT calculations revealed two possible geometric isomers{,} distorted bicapped trigonal antiprism (DBTA) and distorted square antiprism (DSA){,} due to the asymmetry in the chelator. To evaluate the biological behavior of the new bifunctionalization{,} two well-studied PSMA (prostate-specific membrane antigen)-targeting peptidomimetics of varying hydrophobicity were chosen as proof-of-principle targeting vector molecules. Radiolabeling both bioconjugates with lutetium-177 was highly efficient at room temperature in 15 min at micromolar chelator concentration pH = 7. Both the in vitro serum challenge and the lanthanum(III) challenge studies revealed complex lability{,} and notably{,} progressive bone accumulation was only observed with the more hydrophobic linker (i.e. H4octapa-alkyl-PSMA617). This in vivo result informs potential alterations exerted by the linker on the complex geometry and stability{,} with an appropriate biological targeting vector adopted for such evaluations.</p>},
	doi = {10.1039/D0DT00845A},
	url = {http://dx.doi.org/10.1039/D0DT00845A},
	author = {Li, Lily Lee Lee and Kuo, Hsiou-Ting and Wang, Xiaozhu and Merkens, Helen and Colpo, Nadine and Radchenko, Valery and Schaffer, Paul and Lin, Kuo-Shyan and B{\'e}nard, Francois and Orvig, Chris}
}
