Structure-based design and synthesis of a bivalent iminobiotin analog showing strong affinity toward a low immunogenic streptavidin mutant

Kawato, Tatsuya; Mizohata, Eiichi; Shimizu, Y.; Meshizuka, T.; Yamamoto, Tohei; Takasu, Noriaki; Matsuoka, Makoto; Matsumura, Hideki; Kodama, Tatsuhiko; Kanai, Motomu; Doi, Hirofumi; Inoue, Tsuyoshi; Sugiyama, Akira

doi:10.1080/09168451.2014.991692

Cited by 6 publications

(6 citation statements)

References 22 publications

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“…Figure 3 shows the crystal structure of LISA314 V212 in complex with a synthesized bis-iminobiotin analogue, 6-(5-((3aS,4S,6aR)-2-iminohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoic acid (Bis-IMNtail). 17) A surface plasmon resonance assay showed that the Bis-IMNtail has a Kd value of over 8.3 × 10 −10 M toward V212. This was a much higher affinity than that for the monovalent IMNtail (Kd = 5.9 × 10 −7 M).…”

Section: Structure-based Drug Design Of Cupid and Psychementioning

confidence: 99%

“…Amino-acid sequences in the binding pocket of LISA314 in order to increase its affinity to an artificial analogue, iminobiotin using SBDD. 13,16,17)…”

Section: Structure-based Drug Design Of Cupid and Psychementioning

confidence: 99%

“…The resulting mutant, LISA314 V212, showed no binding affinity for biotin and an increase in the affinity for an iminobiotin analogue with a tail (IMNtail) compared with the original LISA314. 13,16,17,19) The crystal structure of LISA314 V212 in complex with two IMNtail molecules indicated that their tails were located very near to each other. 16) In order to increase the binding avidity of its ligand to mutated streptavidin, a bis-form of iminobiotin was designed.…”

Section: Structure-based Drug Design Of Cupid and Psychementioning

confidence: 99%

“…A series of mutant low immunogenic streptavidin forms that do not interact with wild-type biotin but do so strongly with bis-iminobiotins, named Cupids, were selected. 13,16,17) A series of modified bis-iminobiotins with high affinity to Cupid, named Psyches, have been designed and synthesized. Cupids have been fused with scFv, which form tetramers and stay relatively stable in vivo .…”

Section: Introductionmentioning

confidence: 99%

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Cupid and Psyche system for the diagnosis and treatment of advanced cancer

Sugiyama

Kawamura

Tanaka

et al. 2019

Proc. Jpn. Acad., Ser. B

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In advanced cancer patients, malignant cells invade and disseminate within normal cells and develop resistance to therapy with additional genetic mutations, which makes radical cure very difficult. Precision medicine against advanced cancer is hampered by the lack of systems aimed at multiple target molecules within multiple loci. Here, we report the development of a versatile diagnostic and therapeutic system for advanced cancer, named the Cupid and Psyche system. Based on the strong non-covalent interaction of streptavidin and biotin, a low immunogenic mutated streptavidin, Cupid, and a modified artificial biotin, Psyche, have been designed. Cupid can be fused with various single-chain variable fragment antibodies and forms tetramer to recognize cancer cells precisely. Psyche can be conjugated to a wide range of diagnostic and therapeutic agents against malignant cells. The Cupid and Psyche system can be used in pre-targeting therapy as well as photo-immunotherapy effectively in animal models supporting the concept of a system for precision medicine for multiple targets within multiple loci.

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Section: Structure-based Drug Design Of Cupid and Psychementioning

confidence: 99%

“…Amino-acid sequences in the binding pocket of LISA314 in order to increase its affinity to an artificial analogue, iminobiotin using SBDD. 13,16,17)…”

Section: Structure-based Drug Design Of Cupid and Psychementioning

confidence: 99%

Section: Structure-based Drug Design Of Cupid and Psychementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cupid and Psyche system for the diagnosis and treatment of advanced cancer

Sugiyama

Kawamura

Tanaka

et al. 2019

Proc. Jpn. Acad., Ser. B

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“…Regulatory authorities, including the US Food and Drug Administration (FDA), required reliable action to be taken by diagnostic companies to solve this misinterpretation of results caused by biotin interference in clinical assays 8 . Streptavidin variants with low a nity for D-biotin and high a nity for biotin derivatives have been proposed [9][10][11] . However, the a nity for these biotin derivatives have so far proved to be inferior to the a nity of natural streptavidin for D-biotin, showing insu cient applicability of these newly proposed biotin derivatives for avoiding biotin interference.…”

Section: Introductionmentioning

confidence: 99%

Mirror-image Streptavidin with Specific Binding to “Non-natural” L-biotin

Suganuma

Kubo

Ishiki

et al. 2022

Preprint

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The streptavidin-biotin system is known to have a very high affinity and specificity and is widely used in biochemical immunoassays and diagnostics. However, this method is affected by endogenous D-biotin in serum sample measurements (biotin interference). While several efforts using alternative high-affinity binding systems (e.g., genetically modified streptavidin and biotin derivatives) have been attempted, these efforts have all led to reduction in affinity. To solve this interference issue, the enantiomer of streptavidin was synthesized, which enabled specific binding to L-biotin. We successfully obtained a functional streptavidin molecule by peptide synthesis using D-amino acids and an in vitro refolding technique. Several characterizations, including size exclusion chromatography (SEC), circular dichroism spectra (CD), and heat denaturation experiments collectively confirmed the higher-order enantiomer of natural streptavidin had been formed with comparable stability to the natural protein. Non-natural L-biotin specific binding of this novel molecule enabled us to avoid biotin interference in affinity measurements using the Biacore system and enzyme-linked immunosorbent assay (ELISA). We propose the enantiomer of streptavidin as a potential candidate to replace the natural streptavidin-biotin system, even for in vivo use.

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