Single-Bead Quantification of Peptide Loading Distribution for One-Bead One-Compound Library Synthesis Using Confocal Raman Spectroscopy

Yuchen Tang, Yann Thillier, Ruiwu Liu, Xiaocen Li, Kit Lam, Tingjuan Gao

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We report an analytical method to determine peptide loading of "one-bead one-compound" (OBOC) combinatorial peptide libraries at single-bead level. The quantification is based on a linear relationship between the amount of N-terminal amino groups on individual peptide beads and the intensity of Raman signal obtained from a specifically designed reporter labeled on amino groups. Confocal Raman spectroscopy was employed to characterize peptide loading of beads with defined peptide sequences and from OBOC combinatorial peptide libraries. Although amine loading of blank TentaGel beads was found to be uniform, peptide loading among beads of OBOC peptide libraries varied substantially, particularly for those libraries with long sequences. Construction of OBOC libraries can be monitored with this novel analytical technique so that synthetic conditions can be optimized for the preparation of high-quality OBOC peptide libraries. As the variability of peptide loading of individual library beads can significantly influence the screening results, quantitative information obtained by this method will allow us to gain insight into the complexity and challenge of OBOC library synthesis and screening.

Original languageEnglish (US)
Pages (from-to)7000-7008
Number of pages9
JournalAnalytical Chemistry
Volume89
Issue number13
DOIs
StatePublished - Jul 5 2017

ASJC Scopus subject areas

  • Analytical Chemistry

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