Solid-Phase Peptide Synthesis – Evaluation of Resin Loading and Preparation of an Amide C-Terminal Dipeptide (Journal Article)

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Abstract: This communication describes an updated experiment of peptide synthesis, involving determination of the loading capacity of a Fmoc-protected amino functionalized resin using UV–vis spectroscopy and a subsequent synthesis of a dipeptide in order to exemplify the experimental solid-phase synthesis procedure as an alternative technique in organic synthesis. Analysis of the crude dipeptide by liquid chromatography and mass spectrometry is also envisaged. Relevance of solid-phase peptide synthesis (SPPS) to access proteins or small-molecule peptide-based chemical probes is shown to indicate the considerable importance of achieving theoretical and practical skills of a biochemistry/medicinal chemistry graduate in this scientific area. The experiment combines skills in organic and analytical chemistry and focuses on improving students’ abilities to recall knowledge acquired in different disciplines and their use in order to accomplish an experiment, essentially procedurally simple, however, requiring basic theoretical background regarding amino acid reactivity and protecting groups as well as principles of UV–vis spectrophotometric determinations and mass spectrometry. The work may be conveniently split along two laboratory classes or performed at once. In addition, the students can work not only in pairs of two but also in groups containing a greater number because the tasks can be assigned individually.