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Introducing an Asp-Pro Linker in the Synthesis of Random One-Bead-One-Compound Hexapeptide Libraries Compatible with ESI-MS Analysis

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journal contribution
posted on 12.03.2012, 00:00 by Yordanka Masforrol, Jeovanis Gil, Luis Javier González, Yasset Pérez-Riverol, Jorge Fernández-de-Cossío, Aniel Sánchez, Lázaro Hiram Betancourt, Hilda Elisa Garay, Ania Cabrales, Fernando Albericio, Hongqian Yang, Roman A. Zubarev, Vladimir Besada, Osvaldo Reyes Acosta
A random hexapeptide library (one-bead-one-compound), containing sixteen amino acids (166 different sequences) was synthesized on a Tentagel resin previously modified with a dipeptide linker (Asp-Pro). This peptide bond is highly susceptible to cleavage under mild acidic conditions in a salt-free solution prepared with H216O/H218O (60/40% v/v). In the hydrolysis, hexapeptides are released with an additional Asp residue partially labeled with 18O at the C-terminus. These conditions are fully compatible with ESI-MS analysis and facilitate sequencing by MS, as N- and C-terminal ions can be easily differentiated in MS/MS spectra. The peptides were sequenced manually and also with de novo sequencing programs, and identifying them in a database containing all possible heptapeptide sequences or in a filtered database. The proposed strategy is also compatible with stepwise Edman degradation using either intact beads or the released free peptides.