Toward Bioinspired Galectin Mimetics: Identification of Ligand-Contacting Peptides by Proteolytic-Excision Mass Spectrometry

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• 作者：Adrian Moise ; Sabine Andr茅 ; Frederike Eggers ; Mickael Krzeminski ; Michael Przybylski ; Hans-Joachim Gabius
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：September 28, 2011
• 年：2011
• 卷：133
• 期：38
• 页码：14844-14847
• 全文大小：743K
• 年卷期：v.133,no.38(September 28, 2011)
• ISSN：1520-5126

文摘

Clinically relevant bioactivities of human galectins (adhesion/growth-regulatory galactoside-specific lectins) inspired the design of peptides as new tools to elicit favorable effects (e.g., in growth control) or block harmful binding (e.g., in tissue invasion). To obtain the bioinspired lead compounds, we combined a proteolytic fragmentation approach without/with ligand contact (excision) with mass spectrometric identification of affinity-bound protein fragments, using galectin-1 and -3 as models. Two peptides from the carbohydrate recognition domains were obtained in each case in experimental series rigorously controlled for specificity, and the [157鈥?62] peptide of galectin-3 proved to be active in blocking lectin binding to a neoglycoprotein and to tumor cell surfaces. This approach affords peptide sequences for structural optimization and intrafamily/phylogenetic galectin comparison at the binding-site level with a minimal requirement of protein quantity, and it is even amenable to mixtures.