Peptides containing the sulfonamide junction. 2. Structure and conformation of Z-Tau-Pro-D-Phe-NHiPr

• Published in: Biopolymers Vol. 54; no. 6; pp. 379 - 387
• Main Authors: Calcagni, A., Gavuzzo, E., Lucente, G., Mazza, F., Morera, E., Paglialunga Paradisi, M., Rossi, D.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.11.2000
• Subjects: conformation; crystal structure; Crystallography, X-Ray; Drug Design; Enzyme Inhibitors - chemistry; Hydrogen Bonding; Molecular Conformation; Molecular Mimicry; Molecular Structure; nitrogen pyramidalization; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; pseudopeptides; Solubility; sulfonamides; Sulfonamides - chemistry; sulfonamido-peptides; taurine; Taurine - chemistry
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/1097-0282(200011)54:6<379::AID-BIP20>3.0.CO;2-N

The taurine (Tau) containing N‐protected pseudotripeptide isopropylamide Z–Tau–Pro–D‐Phe–NHiPr (1) has been specifically designed and synthesized as suitable model to test the ability of the sulfonamido group to participate as H‐bond acceptor to a type II β‐turn and to get information on the preferred rotameric conformation around the S—N bond and the hybridization state of the nitrogen atom. The present structural investigation reveals that, although the sulfonamide junction is invariably folded in a gauche mode, the β‐turn structure, stabilized by the 4 → 1 hydrogen bond, is not found in the crystal and the sulfonamido oxygen atoms are not involved in any intra‐ or intermolecular hydrogen‐bond interaction. More than one conformer populates the CDCl3 solution with only a minor contribution by the expected β‐turn. The Pro nitrogen is significantly pyramidalized and the nitrogen lone pair points in opposite direction to that of the Pro CαH bond thus adopting R chirality, in an arrangement practically identical to that found in the previously studied homochiral analogue Z–Tau–Pro–Phe–NHiPr. © 2000 John Wiley & Sons, Inc. Biopoly 54: 379–387, 2000