Peptides containing the sulfonamide junction. 2. Structure and conformation of Z-Tau-Pro-D-Phe-NHiPr.
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 beta-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 beta-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 CDCl(3) solution with only a minor contribution by the expected beta-turn. The Pro nitrogen is significantly pyramidalized and the nitrogen lone pair points in opposite direction to that of the Pro C(alpha)H bond thus adopting R chirality, in an arrangement practically identical to that found in the previously studied homochiral analogue Z-Tau-Pro-Phe-NHiPr.
Calcagni
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A
Centro di Studio per la Chimica del Farmaco, CNR c/o Dipartimento di Studi Farmaceutici, Università La Sapienza, 00185 Roma, Italy.
Gavuzzo
E
E
Lucente
G
G
Mazza
F
F
Morera
E
E
Paglialunga Paradisi
M
M
Rossi
D
D
D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D012995:Solubility; D013449:Sulfonamides / Q000737:chemistry*; D013654:Taurine / Q000737:chemistry
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D013449:Sulfonamides; D013654:Taurine