Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides 1 1Edited by I. A. Wilson

Knappik, Achim; Ge, Liming; Honegger, Annemarie; Pack, Peter; Fischer, Melanie; Wellnhofer, Günter; Hoess, Adolf; Wölle, Joachim; Plückthun, Andreas; Virnekäs, Bernhard

doi:10.1006/jmbi.1999.3444

Cited by 696 publications

(491 citation statements)

References 109 publications

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“…1). The VH3 and Vj3 subfamily are the most frequently used genes in the germline [19] and the most stable among VH and VL domains [17]. The amino acid sequence of h3D8 VH and VL FRs, excluding the CDR regions, exhibited 58 and 73% identity to that of m3D8 VH and VL, respectively (Fig.…”

Section: Molecular Modeling Of H3d8 Fvmentioning

confidence: 96%

Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting

Kim

Lee

Kim

et al. 2009

Biochemical and Biophysical Research Communications

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Section: Molecular Modeling Of H3d8 Fvmentioning

confidence: 96%

Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting

Kim

Lee

Kim

et al. 2009

Biochemical and Biophysical Research Communications

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“…Continued technical advances in NGS and in antibody library synthesis have, however, begun to make headway in addressing these technical barriers [reviewed in 53, 113], and a number of fundamental insights into antibody‐antigen affinity and specificity are now apparent: (i) functional antibodies recognize protein‐antigen surfaces mainly through aromatic side chains in their complementarity‐determining regions (CDRs); (ii) the major portion of the antibody‐protein binding energy is contributed by interactions of aromatic side chains from antibody with backbone atoms and side chain‐carbon atoms on protein antigens, which comprise three‐quarters of protein surfaces on average114; (iii) direct hydrogen bonds across the antibody‐antigen interface involve mostly polar backbone groups and small hydrophilic residues on the antibody 114. One implication of these insights is that a synthetic antibody library bearing paratopes with diverse structural contours—enriched with aromatic residues among short chain hydrophilic residues—should be capable of recognizing the surfaces of most protein antigens through binding to common physicochemical features: carbon atoms and polar backbone groups 114…”

Section: Antibodyomics10mentioning

confidence: 99%

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Kwong

Chuang

DeKosky

et al. 2017

Immunological Reviews

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SummaryNumerous antibodies have been identified from HIV‐1‐infected donors that neutralize diverse strains of HIV‐1. These antibodies may provide the basis for a B cell‐mediated HIV‐1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics‐based approach to understand the genetic and immunologic processes controlling the development of HIV‐1‐neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next‐generation sequencing of B‐cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6). We also incorporated large‐scale robotic analyses of serum neutralization to identify and quantify neutralizing antibodies in donor cohorts (Antibodyomics3). Statistical analyses furnish another layer of insight (Antibodyomics5), with physical characteristics of antibodies and their targets through molecular dynamics simulations (Antibodyomics7) and free energy perturbation analyses (Antibodyomics8) providing information‐rich output. Functional interrogation of individual antibodies (Antibodyomics9) and synthetic antibody libraries (Antibodyomics10) also yields multi‐dimensional data by which to understand and improve antibodies. Antibodyomics, described here, thus comprise resolution‐enhancing tools, which collectively embody an information‐driven discovery engine aimed toward the development of effective B cell‐based vaccines.

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“…The diversity is introduced by PCRs with DNA -oligonucleotides having degenerated codons at desired positions. This procedure has the advantage that variations are only allowed in positions essential for antigen binding and by choosing wellexpressed and well-folding frameworks (Pini et al, 1998;Knappik et al, 2000;Sö derlind et al, 2000). Both naïve and semi-synthetic antibody libraries have yielded antibodies with KD's down to the sub-nanomolar range, so both types of libraries -or combinations thereof -can be considered as sources for the selection of antibodies for functional genomics.…”

Section: Phage Antibody Libraries and Formatsmentioning

confidence: 99%

Perspectives for systematic in vitro antibody generation

Konthur

Hust

Dübel

2005

Gene

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After the completion and refinement of the human genome, the characterization of individual gene products in respect of their functions, their modifications, their cellular localization and regulation in both space and time has generated an increased demand for antibodies for their analysis. Taking into account that the human genome contains¨25,000 genes, and that their products are found in different splice variants and produce proteins with post-translational modifications, it can be estimated that at least 100,000 different protein products have to be investigated to gain a complete picture of what's going on in the proteome of a cell.Antibodies are preferred tools helping with the characterization and detection of proteins as well as with elucidating their individual functions. The generation of antibodies to all available human protein products by immunization and/or the hybridoma technology is not only logistically and financially enduring, but may prove to be a difficult task, as quite a number of interesting targets may evade the immune response of experimental animals, for example, allosteric variants dependent on fragile interactions to cofactors, highly conserved antigens etc. For this reason, alternative methods for the generation of antibodies have to supplement these approaches. In vitro methods for antibody generation are seen to offer this capability. In addition, they may provide a cost effective and large scale production alternative for detection reagents for the research community in their own right. Among in vitro techniques, phage display has been evolved as the most efficient option for tackling this problem and approaches optimised for automation are emerging.Maximum benefit for proteomic research could be generated by judicious and preferably international coordination of the ongoing efforts to combine the strengths of the well established animal based approaches and the novel opportunities offered by in vitro methods. D

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Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides 1 1Edited by I. A. Wilson

Cited by 696 publications

References 109 publications

Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting

Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Perspectives for systematic in vitro antibody generation

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