title: Design and synthesis of biotin analogues reversibly binding with streptavidin.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Aoki
authors.forename: Akira
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Doi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
mesh_terms: D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D002384:Catalysis; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D019809:Streptavidin / Q000737:chemistry*
chemical_list: D008670:Metals; D001710:Biotin; D019809:Streptavidin
keywords: biotin; hydrogen bonds; reversible interactions; streptavidin; surface plasmon resonance