Conformational studies of oligomeric oxetane-based dipeptide isosteres derived from L-rhamnose or D-xylose

• Published in: Journal of peptide science Vol. 11; no. 9; pp. 517 - 524
• Main Authors: Johnson, Stephen W., Jenkinson (née Barker), Sarah F., Pérez-Victoria, Ignacio, Edwards, Alison A., Claridge, Timothy D. W., Tranter, George E., Fleet, George W. J., Jones, John H.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-09-2005
• Subjects: Circular Dichroism; conformation; dipeptide isostere; Dipeptides - chemistry; Magnetic Resonance Spectroscopy; oxetane; Protein Conformation; Rhamnose - chemistry; secondary structure; Spectroscopy, Fourier Transform Infrared; Xylose - chemistry
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.658

Conformational investigations have been undertaken on oligomers (dimers, tetramers, hexamers) of five closely related oxetane‐based dipeptide isosteres. All the oligomers were subjected to a range of studies by NMR, FT‐IR and CD spectroscopy. The oligomers derived from methyl 2,4‐anhydro‐5‐azido‐3‐O‐tert‐butyldimethylsilyl‐5‐deoxy‐L‐rhamnonate ‘monomer’ all exhibited evidence of ordered conformations in chloroform and 2,2,2‐trifluoroethanol (TFE) solution. 5‐Acetamido and N‐methylamide derivatives of the L‐rhamnonate ‘monomer’, along with a ‘dimer’ lacking silyl protection at C‐3, were synthesized to ascertain the role of intramolecular interactions. This led to the conclusion that, for the L‐rhamnonate oligomers, steric interactions govern the conformational preference observed. The equivalent silyl‐protected D‐lyxonate oligomers gave ordered CD spectra in TFE solution, but NMR and FT‐IR spectroscopy in chloroform solution suggested an irregular, non‐hydrogen bonded system. The remaining silyl‐protected 6‐deoxy‐L‐altronate, 6‐deoxy‐D‐gulonate and D‐fuconate oligomers appear to be characterized by their lack of ordered conformation in TFE and chloroform solution. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.