Abstract SY06-02: The nontraditional peptide therapeutics

Abstract

Abstract Despite the fact that some peptides had strong affinity or inhibitory activity to certain proteins, because of their poor in-vivo stability there are only a limited number of drugs based on the peptide scaffold to date. However, non-standard peptides, represented by cyclosporine A that is originally isolated as a natural product and developed as an oral available immunosuppressive agent, have remarkable in-vivo stability and membrane permeability, unlike ordinary peptides. To uncover and develop more cyclosporine A-like peptide drugs, it is critical to build a non-traditional strategy involving a system that enables us to discover non-standard peptides quickly and less expensively against a wide variety of intra- and extra-cellular targets. In this talk, I shall introduce a new technology, involving genetic code reprogramming coupled with an in-vitro display, referred to as referred to as RaPID (Random non-standard Peptide Integrated Discovery) system. By means of the RaPID system, we are able to ribosomally express natural product-like peptides containing the features of macrocyclic and N-methylated backbone, and rapidly select highly active sequences against various targets. In this seminar, I shall discuss our recent advance in the discovery of macrocyclic non-standard peptides against EpCAM, Sirt2, E6AP, and JMJD2a, as examples. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY06-02. doi:1538-7445.AM2012-SY06-02