The Enzymatic Degradation of Soluble Bound Biotin

Thoma, R. W.; Peterson, W. H.

doi:10.1016/s0021-9258(18)65383-9

Cited by 72 publications

(6 citation statements)

References 10 publications

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“…We are pursuing the development of radiolabeled biotin derivatives for application to the diagnosis and therapy of cancer using the monoclonal antibody-based "pretargeting method". During our investigations, and similar investigations of other research groups, it has become apparent that it is essential for application of biotin derivatives in vivo that they be designed to block the enzymatic action of the enzyme biotinidase (8,10,23,24). Although biotinidase stabilization is an essential design feature in new biotin reagents for in vivo application, it is also important that biotinidase cleavage be blocked without affecting the high binding affinity of biotin with avidin (Av) and streptavidin (SAv).…”

Section: Discussionmentioning

confidence: 73%

“…Prior to the study, we believed there would be a good likelihood of obtaining biotinidase stability. This belief was based on our previous studies and information in the literature relating to structural features of biotin conjugates and stability toward biotinidase cleavage (10,11,23,(26)(27)(28)(29)(30). Perhaps the most relevant data were reported by Rosebrough, which indicated that an R-carboxylate can block biotinidase activity (11).…”

Section: Discussionmentioning

confidence: 99%

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Biotin Reagents for Antibody Pretargeting. 5. Additional Studies of Biotin Conjugate Design To Provide Biotinidase Stability

et al. 2001

Bioconjugate Chem.

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An investigation was conducted in which the stabilities of four structurally different biotin derivatives were assessed with regard to biotinamide bond hydrolysis by the enzyme biotinidase. The biotin derivatives studied contained an extra methylene in the valeric acid chain of biotin (i.e., homobiotin), or contained conjugated amino acids having hydroxymethylene, carboxylate, or acetate functionalities on a methylene alpha to the biotinamide bond. The biotinidase hydrolysis assay was conducted on biotin derivatives that were radioiodinated at high specific activity, and then subjected to diluted human serum at 37 degrees C for 2 h. After incubation, assessment of biotinamide bond hydrolysis by biotinidase was readily achieved by measuring the percentage of radioactivity that did not bind with avidin. As controls, an unsubstituted biotin derivative which is rapidly cleaved by biotinidase and an N-methyl-substituted biotin derivative which is stable to biotinidase cleavage were included in the study. The results indicate that increasing the distance from the biotin ring structure to the biotinamide bond by one methylene only decreases the rate of biotinidase cleavage, but does not block it. The data obtained also indicate that placing a hydroxymethylene, carboxylate, or acetate alpha to the biotinamide bond is effective in blocking the biotinamide hydrolysis reaction. These data, in combination with data previously obtained, which indicate that biotin derivatives containing hydroxymethylene or carboxylate moieties retain the slow dissociation rate of biotin from avidin and streptavidin [Wilbur, D. S., et al. (2000) Bioconjugate Chem. 11, 569-583], strongly support incorporation of these structural features into biotin derivatives being used for in vivo targeting applications.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Biotin Reagents for Antibody Pretargeting. 5. Additional Studies of Biotin Conjugate Design To Provide Biotinidase Stability

et al. 2001

Bioconjugate Chem.

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“…Indeed, human serum contains large quantities of biotinidase (25 nM), with the concentration being some 12 times higher than both free and bound biotin (24). Although the presence of biotinidase in serum has been known for over four decades (25), until recently (26)(27)(28)(29), it had been generally overlooked in the design of biotin derivatives for in vivo use. This is very important as any instability toward biotinidase cleavage of biotin from radiolabeled biotin derivatives used in pretargeting studies will result in diminished binding.…”

Section: Introductionmentioning

confidence: 99%

Biotin Reagents for Antibody Pretargeting. Synthesis, Radioiodination, and in Vitro Evaluation of Water Soluble, Biotinidase Resistant Biotin Derivatives

et al. 1997

Bioconjugate Chem.

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As part of our development of antibody pretargeting for cancer therapy, an investigation has been conducted to examine the stability of water solubilized, radioiodinated biotin derivatives toward biotinidase degradation in mouse and human serum. Eight new biotin derivatives were synthesized to conduct the study. The biotin derivatives synthesized contained (1) the biotin moiety, (2) a water solubilizing linker moiety, (3) p-iodobenzoate or p-tri-n-butylstannylbenzoate moieties, and (4) in some of the compounds, N-methyl or alpha-methyl containing moieties were added to block biotinidase activity. The linker moiety, 4,7,10-trioxa-1,13-tridecanediamine, 5, was included in the biotin derivatives to improve their water solubility, and it also functioned as a 17 A spacer between the biotin and the benzoyl moieties. Four of the new biotin derivatives (12, 14, 22, and 23) contained a p-tri-n-butylstannylbenzoyl moiety as precursors which could be radioiodinated in the last synthetic step. The other four biotin derivatives (13, 15, 24, and 25) contained p-iodobenzoyl moieties and were used as HPLC reference standards. Initial studies involved radioiodination of 12 to yield [125I]13. Radioiodinated 13, which did not contain a moiety for blocking biotinidase activity, was found to be rapidly degraded in both mouse and human serum at 37 degrees C. Derivatives which were designed to be stable to biotinidase incorporated N-methyl and alpha-methyl moieties adjacent to the biotin carboxylate group. In one set of biotin derivatives (14 and 15), the N-methyl moiety was obtained by incorporating N,N-dimethyl-4,7,10-trioxa-1,13-tridecanediamine, 9, as a linker in the place of 5. In the second set of biotin derivatives (22 and 24), the N-methyl moiety was introduced by incorporating a sarcosine (N-methylglycine) moiety between biotin and 5. The radioiodinated N-methyl containing biotin derivatives [125I]15 and [125I]24 were found to be very stable to biotinidase degradation. An alpha-methyl group was obtained in a pair of biotin derivatives (23 and 25) by incorporating a 3-aminobutyric acid moiety between biotin and 5. The radioiodinated alpha-methyl containing derivative, [125I]25, was found to have an intermediate stability with regards to biotinidase degradation.

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“…Ο ραδιοϊχνηθέτης που παρασκευάσθηκε, είναι ευαίσθητος -λόγω της χημικής του δομής-στη δράση της βιοτινιδάσης, ενζύμου που διασπά τα αμίδια της βιοτίνης (161)(162)(163)(164)(165)(166). Για το λόγο αυτό, οι προς μέτρηση οροί προεπεξεργάζονται με π -OH -υδραργυριβενζοϊκό νάτριο -αντιδραστήριο που ανα στέλλει τη δράση της βιοτινιδάσης (164), χωρίς να επηρεά ζει τα χαρακτηριστικά της ανάλυσης.…”

Section: αναστολέας της βιοτινιδάσηςunclassified

Ραδιοδεσμευτικη Αναλυση Για Τον Προσδιορισμο Βιοτινης Σε Βιολογικα Υγρα

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The Enzymatic Degradation of Soluble Bound Biotin

Cited by 72 publications

References 10 publications

Biotin Reagents for Antibody Pretargeting. 5. Additional Studies of Biotin Conjugate Design To Provide Biotinidase Stability

Biotin Reagents for Antibody Pretargeting. 5. Additional Studies of Biotin Conjugate Design To Provide Biotinidase Stability

Biotin Reagents for Antibody Pretargeting. Synthesis, Radioiodination, and in Vitro Evaluation of Water Soluble, Biotinidase Resistant Biotin Derivatives

Ραδιοδεσμευτικη Αναλυση Για Τον Προσδιορισμο Βιοτινης Σε Βιολογικα Υγρα

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