Recent human genome sequencing has led to the realisation that the family of facilitative sugar transporters (GLUTs: glucose transporters) in mammals is more extensive than the group of five members (GLUTs 1-5) described a decade ago. Now the GLUTs are known to be a more complex family of thirteen isomeric proteins that is divisible into three subgroups based on sequence similarities. 1) Class 1 consists of the glucose transporters (GLUTs 1-4) which preferentially transport D-glucose. 2) Of these transporters GLUT4 is particularly important both in physiological and pathophysiological processes as it is present only in insulin-responsive tissues such as adipose, heart and skeletal muscle. Following insulin signaling, there is an increase in GLUT4 exocytosis from intracellular storage vesicles and incorporation of the protein into the surface membrane of the insulin target cells. 3) Loss of responsiveness of this protein to insulin is one of the contributing factors to the pathogenesis of Type 2 diabetes. 4) To effectively examine the mechanisms involved in exposure of GLUT4 at the cell surface of adipocytes, high affinity analogues that can tag the transporter are required. Synthesizing suitable analogues is a difficult task since sugars have relatively low affinity for the transporter molecules. D-Glucose for example, when interacting with GLUT4, does so with an affinity constant (K m ) of around 8 mM. Physiologically the high K m is important as if the affinity for D-glucose were very high then this substrate would bind very strongly to the transporter rather than being transported through it. In addition, blood glucose levels are generally 5 mM (or slightly higher following a carbohydrate rich meal) and therefore a high affinity (low K m ) system would become too easily saturated and unable to respond to the fluctuations in circulating blood glucose levels. The requirements for a GLUT4 tag are opposite to these and high affinity interaction is required in a photolabel as the ligand/protein complex has to be occupied at a high enough level to be efficiently converted to a covalent complex following UV irradiation. 5) We have developed a series of photoaffinity probes based on bis-hexose structures. 6) These compounds contain hexoses linked via their 4-OH positions to a propyl-2-amine spacer. Because the bis-hexose structure renders the compounds large and hydrophilic the derivatives are impermeant and just probe those glucose transporters (GLUT4) that appear at the cell-surface in response to insulin. We have already synthesized photoreactive bis-mannose derivatives containing arylazide, 7) benzophenone 8) and 3-phenyl-3-trifluoromethyldiazirine 9) substitutions for use in glucose transporter cell surface labeling. Recently, we have synthesized photoreactive bis-glucose derivatives containing the 3-phenyl-3-trifluoromethyldiazirine group. 10) These can easily be synthesised preparative scale and have slightly higher affinity for GLUT4 than the equivalent bis-mannose compounds.Arylazide ligands were found to b...