Investigations into self-association of vancomycin covalent dimers using surface plasmon resonance technology

Adamczyk, Maciej; Moore, Jeffrey A.; Rege, Sushil; Yu, Zhiguang

doi:10.1016/s0960-894x(99)00402-3

Cited by 21 publications

(17 citation statements)

References 14 publications

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“…Types of previously synthesized vancomycin dimers: a) Griffin [13] and Whitesides [14] (head-to-head); b) Williams [15] (head-to-tail), c) Abbott [16] and Eli Lilly [17] groups (back-to-back).…”

Section: Resultsmentioning

confidence: 99%

“…[14] Perhaps, however, of more biological relevance are the head-to-tail dimers. Constructs of this type were synthesized by the Williams group, [15] linking from the C-terminus to the N-terminus, and by groups at Abbott [16] and Eli Lilly, [17] both bridging their monomeric units through the vancosamine nitrogen. Finally, a vancomycin-derived trimer [18] has been reported as well as an oligomeric system, [19] the latter exhibiting improved bacteriacidal activity against vancomycin-resistant strains.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Biological Evaluation of Vancomycin Dimers with Potent Activity against Vancomycin-Resistant Bacteria: Target-Accelerated Combinatorial Synthesis

et al. 2001

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Based on the notion that dimerization and/or variation of amino acid 1 of vancomycin could potentially enhance biological activity, a series of synthetic and chemical biology studies were undertaken in order to discover potent antibacterial agents. Herein we describe two ligation methods (disulfide formation and olefin metathesis) for dimerizing vancomycin derivatives and applications of target-accelerated combinatorial synthesis (e.g. combinatorial synthesis in the presence of vancomycin's target Ac2-L-Lys-D-Ala-D-Ala) to generate libraries of vancomycin dimers. Screening of these compound libraries led to the identification of a number of highly potent antibiotics effective against vancomycin-suspectible, vancomycin-intermediate resistant and, most significantly, vancomycin-resistant bacteria.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Vancomycin Dimers with Potent Activity against Vancomycin-Resistant Bacteria: Target-Accelerated Combinatorial Synthesis

et al. 2001

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“…26,27 A variety of analytical techniques are available to detect and characterize self-association. These techniques include but are not limited to proton magnetic relaxation dispersion, 28,29 surface plasmon resonance, 30,31 isothermal titration calorimetry, 32 nuclear magnetic resonance, 33 fluorescence energy transfer, 34 mass spectrometry, 35 self-interaction nano-particle spectroscopy, 36 analytical ultracentrifugation (AUC), 20,37 dynamic light scattering (DLS), and composition-gradient multiangle static light scattering (CG-MALS). [38][39][40][41] The choice of the employed analytical techniques, not only based on their capabilities and complementarities but more importantly their suitability for a given stage of development, is an important factor for successful evaluation of RSA.…”

Section: Introductionmentioning

confidence: 99%

A systematic multitechnique approach for detection and characterization of reversible self-association during formulation development of therapeutic antibodies

Esfandiary¹,

Hayes²,

Parupudi³

et al. 2013

Journal of Pharmaceutical Sciences

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In addition to controlling typical instabilities such as physical and chemical degradations, understanding monoclonal antibodies' (mAbs) solution behavior is a key step in designing and developing process and formulation controls during their development. Reversible self-association (RSA), a unique solution property in which native, reversible oligomeric species are formed as a result of the noncovalent intermolecular interactions has been recognized as a developability risk with the potential to negatively impact manufacturing, storage stability, and delivery of mAbs. Therefore, its identification, characterization, and mitigation are key requirements during formulation development. Considering the large number of available analytical methods, choice of the employed technique is an important contributing factor for successful investigation of RSA. Herein, a multitechnique (dynamic light scattering, multiangle static light scattering, and analytical ultracentrifugation) approach is employed to comprehensively characterize the self-association of a model immunoglobulin G1 molecule. Studies herein discuss an effective approach for detection and characterization of RSA during biopharmaceutical development based on the capabilities of each technique, their complementarity, and more importantly their suitability for the stage of development in which RSA is investigated.

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“…The study indicated that the biological activity of such covalent dimers is correlated to their ability to self-assemble (that is, to adopt the back-to-back conformation). [30] On the basis of the structure of the back-to-back dimer (Scheme 2 b) we reasoned that the most appropriate means by which to form such a stable dimer would be to construct a bridge across the saccharide domains of two vancomycin molecules. However, selecting the appropriate tether so as to permit the full cooperation of the two monomers in forming the desired back-to-back arrangement was the more demanding challenge.…”

mentioning

confidence: 99%

Target-Accelerated Combinatorial Synthesis and Discovery of Highly Potent Antibiotics Effective Against Vancomycin-Resistant Bacteria

Nicolaou

Hughes

Cho

et al. 2000

Angew. Chem. Int. Ed.

150

100

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Biological activity can be predicted at a prescreening stage by using a target‐accelerated combinatorial synthesis. The rate of dimerization of vancomycin analogues (see picture, X=CH=CH2, SAc) in the presence of vancomycin's targets Ac‐D‐Ala‐D‐Ala and Ac2‐L‐Lys‐D‐Ala‐D‐Ala correlated well with the observed biological activity. From this study three highly potent antibacterial agents effective against both vancomycin‐susceptible and vancomycin‐resistant bacteria strains were identified.

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Investigations into self-association of vancomycin covalent dimers using surface plasmon resonance technology

Cited by 21 publications

References 14 publications

Synthesis and Biological Evaluation of Vancomycin Dimers with Potent Activity against Vancomycin-Resistant Bacteria: Target-Accelerated Combinatorial Synthesis

Synthesis and Biological Evaluation of Vancomycin Dimers with Potent Activity against Vancomycin-Resistant Bacteria: Target-Accelerated Combinatorial Synthesis

A systematic multitechnique approach for detection and characterization of reversible self-association during formulation development of therapeutic antibodies

Target-Accelerated Combinatorial Synthesis and Discovery of Highly Potent Antibiotics Effective Against Vancomycin-Resistant Bacteria

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