The syntheses and in vivo biodistribution of novel boronated unnatural amino acids.
A series of boronated, unnatural amino acids were prepared and their biodistribution determined in melanoma bearing mice. The unnatural amino acids were prepared utilizing recently developed borylation. The majority of the syntheses utilize metal catalyzed additions of diboron agents to unsaturated carbonyl compounds. Biodistribution studies in mice bearing melanoma tumors indicated that all the boronated amino acids were taken up by the melanoma tumors. The data for the cyclic five-membered ring analogue, 1-amino-3-boronocyclopentanecarboxylic acid, was most striking, exhibiting a nearly 22:1 ratio of boron concentration for tumor to brain at the 2 h time point, dropping to 7.3 after 6 h. The tumor to blood and tumor to skin ratios were also quite high. It is important to note that all of the amino acids were synthesized as racemic and diastereomeric mixtures. Thus there is a high probability that a single enantiomer of 1-amino-3-boronocyclopentanecarboxylic acid might exhibit far higher selectivity.
Kabalka
G W
GW
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA. kabalka@utk.edu
Wu
Z Z
ZZ
Yao
M-L
ML
Natarajan
N
N
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D005260:Female; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D014018:Tissue Distribution
D000596:Amino Acids; D001896:Boron Compounds