Bodanszky M, Tolle J C, Bednarek M A, Schiller P W
Int J Pept Protein Res. 1981 Apr;17(4):444-53. doi: 10.1111/j.1399-3011.1981.tb02013.x.
The hormone analog 8-L-tryptophan-oxytocin was synthesized in solution by stepwise chain lengthening from the C-terminal residue. Active esters of 9-fluorenylmethyloxycarbonyl (Fmoc)-amino acids were used for the incorporation of individual residues and thereby exposure to the tryptophan-containing intermediates both to acid conditions and to alkylation could be avoided. In a parallel experiment the parent compound, oxytocin, was prepared similarly. The final products were purified by countercurrent distribution. The presence of tyrosine (donor) and tryptophan (acceptor) in the chain was used for the measurement of the average intramolecular Tyr2-Trp8 distance by evaluation of intramolecular resonance energy transfer between their fluorescent side chains. Since the 8-L-tryptophan analog has high affinity for oxytocin receptors, it is reasonable to assume that its conformation is similar to that of the parent molecule and that in the latter the leucine-tyrosine distance is of about the same length. The distance of 13.5 Ao between the side chains of tyrosine and tryptophan measured in aqueous solution is compatible with the Tyr2-Leu8 distance determined with molecular models built according to the proposals of Walter for the biologically active conformation of oxytocin.
