Towards better solid-phase peptide synthesis and screening: Ideal resins and tagging (#7)
For efficient SPPS, we have proposed several kinds of core―shell-type resin in which reactive functional groups are mainly located on shell layer of the resin [1-6] The core―shell (CS) structure was designed to overcome the diffusion problem and for easy accessibility of reagents. Because of this distinctive structural feature, the CS type resins afforded high performance in peptide synthesis and photolytic cleavage reactions. These resins were prepared by suspension co-polymerization, two-step polymerization, cross-linking core domain, partial hydrolysis, and biphasic functionalization methods. To evaluate the performance of CS type resins, “difficult” sequence peptides were synthesized, and the results were compared with those of non CS type AM PS resin and PEG-based resins.
Recently, the preparation and screening of compound libraries remain one of the most challenging tasks in drug discovery, biomarker detection, and biomolecular profiling processes. So far, several distinct encoding/decoding methods such as chemical encoding, graphical encoding, and optical encoding have been reported to identify those libraries. For efficient peptide library encoding, surface-enhanced Raman scattering (SERS) based encoding method was developed, which involves highly sensitive SERS nanopaticles (so called SERS dots). Peptides were synthesized on TentaGel (TG) resin by using Fmoc chemistry. During peptide coupling, the TG resins were encoded by the combination of several kinds of SERS dots, which are physically adsorbed on the resin bead surface. [7] When the resin bead was encoded by the combination of 5 kinds of the SERS dots, more than 300,000 codes can be generated. The advantages of the SERS dots based encoding method lies in the availability of a large number of Ramam active molecules which can be utilized as Raman label compounds. Moreover, the SERS signals have narrow band width (< 1 nm) without peak overlap, and a single excitation is used for the detection of multiple encodings.
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