Latest Advances in OBOC Peptide Libraries. Improvements in Screening Strategies and Enlarging the Family From Linear to Cyclic Libraries

Abstract

Solid phase screenings of one bead one compound (OBOC) libraries have been widely used to find ligands with pharmacological and analytical uses, and to purify or detect proteins in complex mixtures. To improve library screening, in the last years various strategies have been developed to avoid the selection of false positive beads and to obtain selective ligands. Currently, there is great interest in cyclic peptides because of their resistance to enzymatic degradation and higher selectivity compared to their linear counterparts. Lots of cyclic peptide libraries protocols have been recently developed to facilitate hits analysis. The aim of this review is to summarize the latest applications of solid phase screening of OBOC combinatorial peptide libraries, the improvements in the screening methods including mass spectrometry MS/MS techniques and the strategies to synthesize OBOC cyclic peptide libraries.

Insight into the Development of PET Radiopharmaceuticals for Oncology

“…To identify hits in a complex mixture of compounds, screening strategies include DNA-encoded libraries [150][151][152][153], biological libraries (e.g., phage-display) [154][155][156][157][158][159], and one-bead-one-compound (OBOC) libraries [160,161]. These strategies construct pharmacophores by ligating discrete building blocks of chemicals.…”

Combinatorial Library Screening Coupled to Mass Spectrometry to Identify Valuable Cyclic Peptides

“…As we have recently reviewed (Martínez‐Ceron et al., ), there has been much interest in the development of OBOC combinatorial cyclic‐peptide libraries, and many protocols have been developed for synthesis of OBOC combinatorial cyclic‐peptide libraries using on‐resin homodetic cyclization.…”

“…Based on these critical points, the use of peptides as therapeutic drugs or as ligands for affinity chromatography is promising (Joo, ). Although functional cyclic peptides may be found in natural sources, screening of combinatorial peptide libraries synthesized using natural and unnatural amino acids facilitates the discovery of a more diverse array of functional peptides for any given purpose (Martínez‐Ceron et al., ).…”

Bottom-Up Design Approach for OBOC Peptide Libraries

“…OBOC combinatorial libraries allow the synthesis of large and diverse mixtures of peptide sequences and their concurrent screening for affinity interactions [ 1 , 2 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. The four main steps employed in the development of OBOC peptide libraries are: (a) library synthesis, (b) screening against biological targets of interest, (c) deconvolution of the sequence, followed by (d) validation of peptide entities [ 19 ].…”

“…Several examples have been developed and characterized following this scheme [ 12 , 16 , 20 , 21 , 22 ]. In addition, a variety of optimized methods have been proposed to improve both synthesis and screening processes, such as the use of color coding [ 23 ], fluorescent dyes [ 17 ], immobilization of beads on solid supports [ 24 ] and others [ 3 , 14 , 18 , 21 , 25 ]. This typical top-down design approach to OBOC peptide libraries leads to the efficient synthesis of large libraries but often fails in the step of sequence identification after screening.…”