Solid-Phase Peptide Synthesis - Evaluation of Resin Loading and Preparation of an Amide C-Terminal Dipeptide

This communication describes an updated experiment ofpeptide synthesis,involving determination of the loading capacity of a Fmoc-protectedamino functionalized resin using UV-vis spectroscopy and asubsequent synthesis of a dipeptide in order to exemplify the experimentalsolid-phase synthesis procedure as an alternative technique in organicsynthesis. Analysis of the crude dipeptide by liquid chromatographyand mass spectrometry is also envisaged. Relevance of solid-phasepeptide synthesis (SPPS) to access proteins or small-molecule peptide-basedchemical probes is shown to indicate the considerable importance ofachieving theoretical and practical skills of a biochemistry/medicinalchemistry graduate in this scientific area. The experiment combinesskills in organic and analytical chemistry and focuses on improvingstudents' abilities to recall knowledge acquired in differentdisciplines and their use in order to accomplish an experiment, essentiallyprocedurally simple, however, requiring basic theoretical backgroundregarding amino acid reactivity and protecting groups as well as principlesof UV-vis spectrophotometric determinations and mass spectrometry.The work may be conveniently split along two laboratory classes orperformed at once. In addition, the students can work not only inpairs of two but also in groups containing a greater number becausethe tasks can be assigned individually.