Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10-6M and 1.7×10-10M, respectively. These values were remarkably greater than that of biotin (KD=10-15M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin.
CITATION STYLE
Yamamoto, T., Aoki, K., Sugiyama, A., Doi, H., Kodama, T., Shimizu, Y., & Kanai, M. (2015). Design and synthesis of biotin analogues reversibly binding with streptavidin. Chemistry - An Asian Journal, 10(4), 1071–1078. https://doi.org/10.1002/asia.201500120
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