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1.
Biotechnol Adv ; 47: 107699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33513435

RESUMO

Innovative biotechnological methods empower the successful identification of new drug candidates. Phage, ribosome and mRNA display represent high throughput screenings, allowing fast and efficient progress in the field of targeted drug discovery. The identification range comprises low molecular weight peptides up to whole antibodies. However, a major challenge poses the stability and affinity in particular of peptides. Chemical modifications e.g. the introduction of unnatural amino acids or cyclization, have been proven to be essential tools to overcome these limitations. This review article particularly focuses on available methods for the targeted chemical modification of peptides and peptide libraries in selected display approaches.


Assuntos
Biblioteca de Peptídeos , Peptídeos , Descoberta de Drogas , Ensaios de Triagem em Larga Escala , Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional
2.
Methods ; 65(1): 57-67, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24036249

RESUMO

Over the last nearly three decades in vitro display technologies have played an important role in the discovery and optimization of antibodies and other proteins for therapeutic applications. Here we describe the use of retroviral expression technology for the display of full-length IgG on B lineage cells in vitro with a hallmark of a tight and stable genotype to phenotype coupling. We describe the creation of a high-diversity (>1.0E09 different heavy- and light-chain combinations) cell displayed fully human antibody library from healthy donor-derived heavy- and light-chain gene libraries, and demonstrate the recovery of high affinity target-specific antibodies from this library by staining of cells with a labeled target antigen and their magnetic- and flow cytometry-based cell sorting. The present technology represents a further evolution in the discovery of full-length, fully human antibodies using mammalian display, and is termed Retrocyte Display® (Retroviral B lymphocyte Display).


Assuntos
Anticorpos Monoclonais/biossíntese , Retroviridae/genética , Animais , Anticorpos Monoclonais/genética , Linfócitos B/metabolismo , Criopreservação , Avaliação Pré-Clínica de Medicamentos , Citometria de Fluxo , Variação Genética , Vetores Genéticos , Células HEK293 , Humanos , Cadeias Pesadas de Imunoglobulinas/biossíntese , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/biossíntese , Cadeias Leves de Imunoglobulina/genética , Separação Imunomagnética , Biblioteca de Peptídeos , Ligação Proteica
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