Bottom-Up Design Approach for OBOC Peptide Libraries

One-bead-one-compound peptide libraries, developed following the top-down experimental approach, have attracted great interest in the identification of potential ligands or active peptides. By exploiting a reverse experimental design approach based on the bottom-up strategy, we aimed to develop simp...

Descripción completa

Detalles Bibliográficos
Autores: Kalafatovic, Daniela, Mausa, Goran, Resetar Maslov, Dina, Giralt Lledó, Ernest
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/174930
Acceso en línea:https://hdl.handle.net/2445/174930
Access Level:acceso abierto
Palabra clave:Síntesi de pèptids
Síntesi en fase sólida
Química combinatòria
Peptide synthesis
Solid-phase synthesis
Combinatorial chemistry
Descripción
Sumario:One-bead-one-compound peptide libraries, developed following the top-down experimental approach, have attracted great interest in the identification of potential ligands or active peptides. By exploiting a reverse experimental design approach based on the bottom-up strategy, we aimed to develop simplified, maximally diverse peptide libraries that resulted in the successful characterization of mixture components. We show that libraries of 32 and 48 components can be successfully detected in a single run using chromatography coupled to mass spectrometry (UPLC-MS). The proposed libraries were further theoretically evaluated in terms of their composition and physico-chemical properties. By combining the knowledge obtained on single libraries we can cover larger sequence spaces and provide a controlled exploration of the peptide chemical space both theoretically and experimentally. Designing libraries by using the bottom-up approach opens up the possibility of rationally fine-tuning the library complexity based on the available analytical methods.