Vitamin B12 monocarboxylic acids: unambiguous isomer assignments by modern two-dimensional NMR spectroscopy

Pagano, Thomas G.; Marzillï, Luigi G.

doi:10.1021/bi00444a013

Cited by 24 publications

(18 citation statements)

References 37 publications

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“…Mild acid hydrolysis of (CN)Cbl ( 1 a ) leads to a mixture of the corresponding monocarboxylic acids 13 a ‐ c at the b , d , e‐ positions, respectively, along with di‐ and tricarboxylic derivatives (Scheme ) ,. Although yields are far from satisfactory and the purification process remains laborious, the access to monoacids 13 has opened new vistas for tethering cargoes at the periphery of the macrocycle.…”

Section: Conjugation At the Macrocyclic Corementioning

confidence: 99%

Synthetic Approaches toward Vitamin B₁₂ Conjugates

2018

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The ability to conjugate functional molecules to vitamin B 12 (cobalamin) is an important strategy for the construction of hybrid molecules with various applications in medicinal chemistry, diagnostics, and biological sciences. Cobalamin, as an exogenous compound, reaches mammalian cells via a system of transport proteins and therefore the position of conjugation must be selected in such a way that the recognition process is not disturbed. The complex structure of vitamin B 12 provides many routes for the synthesis of conjugates containing cargos appended at different sites, however, only the e-propionamide chain, βaxial position and R 5' -OH are found to meet the aforementioned criteria. Over the years, a number of synthetic approaches leading to cobalamin conjugates have been developed and, herein, we summarize those leading to conjugates with a cargo tethered at the central cobalt ion, macrocyclic core, ribonucleotide moiety, or a combination thereof. . Synthesis of cobalamin triazoles. Scheme 16. Synthesis of precursor 41 and its subsequent functionalization. Scheme 17. Functionalization of phosphate moiety.[a] Compound 43 c was obtained from 43 b via substitution with NaN 3 .

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Section: Conjugation At the Macrocyclic Corementioning

confidence: 99%

Synthetic Approaches toward Vitamin B₁₂ Conjugates

2018

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“…[26,28] Subsequent neutron diffraction studies indicated that it could be the bacid, an assumption that was later confirmed by sophisticated multi-dimensional NMR measurements. [29][30][31][32] The similar diffraction power of the OH and NH 2 groups was the problem in X-ray analysis. Cobalamin crystals were rarely obtained in the quality required for an unambiguous differentiation between these two groups.…”

Section: Synthesesmentioning

confidence: 99%

Structures of the b‐ and d‐Acid Derivatives of Vitamin B₁₂ and Their Complexes with [M(CO)₃]⁺ (M = ^99mTc, Re)

et al. 2007

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The acid hydrolysis of natural vitamin B 12 yields several products in which the acetamide or propionamide side chains on the corrin framework are converted into the corresponding acids. These acids can be derivatised with further functionalities. We have separated in particular the b-and the dacid derivatives 1 and 2, respectively, since functionalisation at these positions of the corrin ring generally keeps the affinity for vitamin B 12 transport proteins intact. Although the authenticity of 1 and 2 seemed evident from 1 H NMR investigations, it has not been supported by X-ray structure analysis. The coupling of ethyl N-(3-aminopropyl)-N-(pyridin-2-ylmethyl)glycinate (3) to the carboxylate groups in 1 and 2 by

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“…However, previous in-vestigators have shown that NMR could be used to distinguish the isomers (58,59). Assignments were still somewhat ambiguous until an elaborate set of NMR experiments were conducted to assign all of the 1 H and 13 C resonances of two of the three isomers (b-and e-; dwas insoluble in adequate quantities for the experiment), and those assignments were used to correlate their connectivities in two-dimensional NMR spectroscopy with structures (60). That study unambiguously assigned structures to all three isomers (d-isomer by default).…”

Section: Preparation Of Corrin Ring B- D- and E-carboxylate Conjugate...mentioning

confidence: 99%

Synthesis of Cobalamin−Biotin Conjugates That Vary in the Position of Cobalamin Coupling. Evaluation of Cobalamin Derivative Binding to Transcobalamin II

et al. 1996

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Six cobalamin-biotin conjugates have been prepared. The cobalamin-biotin conjugates were prepared to evaluate the effect that the location of attachment had on the binding with transcobalamin II (TCII), the cobalamin binding protein in plasma, and to evaluate their potential use for in vitro and in vivo applications. This study focused only on the effect of binding with TCII. To decrease the possibility of steric problems in binding of the cobalamin conjugates with TCII, and biotin's binding with streptavidin or avidin, moieties of 11-18 atoms in length were used as linkers. Four biotin conjugates were prepared which were attached to the corrin ring of the cobalamin molecule (on b-, c-, d-, and e-side chains). One conjugate was attached to the 5'-OH of the ribose moiety, and another conjugate was attached at the cobalt metal (in place of the cyanide moiety of cyanocobalamin). Competitive binding studies were conducted where various amounts of the cobalamin-biotin conjugates and their precursor cobalamin derivatives competed with [57Co]cyanocobalamin for binding of recombinant human TCII (rhTCII). Evaluation of cobalamin derivatives which were conjugated at the 5'-OH of ribose or the cobalt metal center indicated that conjugation at either of these positions had little effect on binding with rhTCII. However, conjugates where the attachment was made on the corrin ring substituents had a large variation in binding with rhTCII. Conjugates on the e-propionamide side chain had little effect (relative affinity was equal to or decreased less than a factor of 3) on binding with rhTCII, conjugates of the b-isomer had decreased binding (relative affinity decreased less than a factor of 10), conjugates of the d-propionamide had further decreased binding (relative affinity decreased between 44 and 69 times), and conjugates on the c-acetamide group had poor binding to rhTCII (relative affinity decreased between 295 and 1160 times). The significance of the side chains on the corrin ring in providing specificity and high-affinity binding with rhTCII is discussed.

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Vitamin B12 monocarboxylic acids: unambiguous isomer assignments by modern two-dimensional NMR spectroscopy

Cited by 24 publications

References 37 publications

Synthetic Approaches toward Vitamin B₁₂ Conjugates

Synthetic Approaches toward Vitamin B₁₂ Conjugates

Structures of the b‐ and d‐Acid Derivatives of Vitamin B₁₂ and Their Complexes with [M(CO)₃]⁺ (M = ^99mTc, Re)

Synthesis of Cobalamin−Biotin Conjugates That Vary in the Position of Cobalamin Coupling. Evaluation of Cobalamin Derivative Binding to Transcobalamin II

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Vitamin B12 monocarboxylic acids: unambiguous isomer assignments by modern two-dimensional NMR spectroscopy

Cited by 24 publications

References 37 publications

Synthetic Approaches toward Vitamin B12 Conjugates

Synthetic Approaches toward Vitamin B12 Conjugates

Structures of the b‐ and d‐Acid Derivatives of Vitamin B12 and Their Complexes with [M(CO)3]+ (M = 99mTc, Re)

Synthesis of Cobalamin−Biotin Conjugates That Vary in the Position of Cobalamin Coupling. Evaluation of Cobalamin Derivative Binding to Transcobalamin II

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Synthetic Approaches toward Vitamin B₁₂ Conjugates

Synthetic Approaches toward Vitamin B₁₂ Conjugates

Structures of the b‐ and d‐Acid Derivatives of Vitamin B₁₂ and Their Complexes with [M(CO)₃]⁺ (M = ^99mTc, Re)