Peptides containing the sulfonamide junction: Synthesis, structure, and conformation of Z-Tau-Pro-Phe-NHiPr

Abstract

The taurine (Tau) containing tripeptide derivative Z‐Tau‐Pro‐Phe‐NHiPr (1) has been synthesized as suitable sulfonamido‐pseudopeptide model to investigate formation and conformational properties of folded secondary structures stabilized by intramolecular H bonds directly involving the sulfonamide junction. In the crystal the pseudopeptide 1 adopts a type I β‐turn with the Pro and Phe residues located at the (i + 1) and (i + 2) corner positions, respectively. The turn is stabilized by a 4 → 1 H bond engaging one of the SO2 oxygen atoms and the isopropylamide NH. In CDCl3 solution the β‐turn folding is accompanied by a γ‐turn centered at the Pro and involving a 3 → 1 H bond between the SO2 and the Phe NH. A comparison of the structural and conformational properties found in 1 with those of the already known sulfonamido‐pseudopeptides, with particular reference to the models containing the Tau‐Pro junction, is also reported. © 1997 John Wiley & Sons, Inc. Biopoly 41: 555–567, 1997.

Structural Insight into the Stereoselective Inhibition of MMP-8 by Enantiomeric Sulfonamide Phosphonates

“…Several crystallographic investigations show the preference for the gauche conformations. [48][49][50][51] In accordance, the two complexed R-and S-enantiomers adopt the g + (72°) and g -(-89°) conformation, respectively. As a consequence, while the sulfonamide NH group of the R-enantiomer is turned toward the upper rim, giving rise to a H-bond (3.0 Å) with the A161 CO group, the same NH of the S-enantiomer faces the solvent, engaging a H-bond (3.0 Å) with a water molecule.…”

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

“… Stereo view of the homochiral pseudotripeptide Z—Tau—Pro—Phe—NHiPr (see Ref. 1). For clarity, only the H atoms bound to the nitrogen and chiral C α atoms have been indicated.…”

“…Our studies on this class of oligopeptides1, 4–9 tend to acquire information on the propensity to give rise to folded structures directly involving the sulfonamido group as well as on some structural features of this junction such as the preferred rotameric conformation around the S—N bond and the hybridization state of the nitrogen atom. Several findings put in evidence the interest of this topic and the relevance of the pyramidal nitrogen sulfonamides to design peptide mimics or new structural motifs 29, 30…”

Two Crystal Structures of Human Neutrophil Collagenase, One Complexed with a Primed- and the Other with an Unprimed-Side Inhibitor: Implications for Drug Design

“…To account for its low K i value, the entropic advan- tage deriving from the conformational constraints present in this inhibitor should be considered. The restrictions involve: (i) the D-Tic residue, a Phe analogue showing only grotamers for χ 1 and orientation of the aromatic ring almost perpendicular to that preferred 49 by Phe, Tyr, and Trp; (ii) the gsulfonamide junction [23][24][25][26] properly directing the biphenyl group into the deep S 1 ′ pocket; and (iii) the biphenyl group adopting an average dihedral angle of about 30°between the two rings. 50 PLTP Binding at the S Region of MMP-8.…”

“…The primed-side inhibitor is (R) -2-(biphenyl-4-ylsulfonyl)-1,2,3,4-tetrahydroisochinolin-3-carboxylic acid. , This simple d -Tic − derivative (TIC) attracted our attention because of its nanomolar inhibitory activity against HNC, despite the following unfavorable features: (i) 1,3-bidentate or monodentate zinc binding by the carboxylate group which is generally weaker than the 1,4-bidentate hydroxamate group; (ii) lack of peptide groups, generally engaged in H-bonds with the enzyme active site, thus providing a reduced number of interactions compared to di- and tripeptide hydroxamates; and (iii) noncomplementarity with the collagenase extended binding region, due to the constrained folded conformation of the sulfonamide junction which is populated only by gauche conformers. − While our work was in progress, the crystal structure of this inhibitor complexed with a differently truncated form of MMP-8 (Gly99−Glu271) was reported and validated the docking calculations performed on a large series of Tic derivatives in the catalytic domain of MMP-8. Here we report our X-ray structure results at the higher resolution of 1.2 Å and describe the implications of our detailed investigation on drug-binding and design studies.…”