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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• 作者：Yordanka Masforrol ; Jeovanis Gil ; Luis Javier Gonz谩lez ; Yasset P茅rez-Riverol ; Jorge Fern谩ndez-de-Coss铆o ; Aniel S谩nchez ; L谩zaro Hiram Betancourt ; Hilda Elisa Garay ; Ania Cabrales ; Fernando Albericio ; Hongqian Yang ; Roman A. Zubarev ; Vladimir Besada ; Osvaldo Reyes Acosta
• 刊名：ACS Combinatorial Science
• 出版年：2012
• 出版时间：March 12, 2012
• 年：2012
• 卷：14
• 期：3
• 页码：145-149
• 全文大小：289K
• 年卷期：v.14,no.3(March 12, 2012)
• ISSN：2156-8944

文摘

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.

Keywords:

peptide library; one-bead-one-compound; tentagel; mass spectrometry; electrospray ionization; de novo sequencing