Design and synthesis of biotin analogues reversibly binding with streptavidin.

Authors:
Tomohiro Yamamoto
Tomohiro Yamamoto
Niigata University Graduate School of Medicine and Dental Sciences
Kiyoshi Aoki
Kiyoshi Aoki
Life Science Institute
Japan
Akira Sugiyama
Akira Sugiyama
The University of Tokyo
Japan
Hirofumi Doi
Hirofumi Doi
The University of Tokyo
Bunkyo | Japan
Tatsuhiko Kodama
Tatsuhiko Kodama
The University of Tokyo
Japan
Yohei Shimizu
Yohei Shimizu
Graduate School of Pharmaceutical Sciences
Japan
Motomu Kanai
Motomu Kanai
Graduate School of Pharmaceutical Sciences
Japan

Chem Asian J 2015 Apr 5;10(4):1071-8. Epub 2015 Mar 5.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).

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(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin.

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April 2015
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