A previously unknown protein produced by an mRNA mutation has recently been identified in Alzheimer's patients. The protein, designated UbN, is composed of the first 75 residues of ubiquitin followed by an unrelated sequence of 20 residues. The synthesis of this 10.7kDa entity was carried out, as well as its purification which was based on a novel affinity support in conjunction with the tetrabenzofluoroene moiety. In vitro testing established how the protein could compromise the ubiquitin-dependent proteolytic system, hence exerting a toxic effect in Alzheimer's patients. The synthesis of an analogue of ubiquitin (76 residues, 8.5kDa), which contained the unnatural amino acid 2S, 4S-5-fluoroleucine in place of leucine at the 50 and 67 positions, has been carried out. A short purification and folding protocol was developed, and comparison of the analogue with the native structure was undertaken. A possible application of the analogue in the study of protein folding using ¹⁹F nmr has been examined.