Monica Pantano

Position of side-chain branching and handedness of turns and helices of homopeptides from chiral Cα-methylated amino acids. Crystal-state structural analysis of (αMe)Leu trimer and tetramer

Terminally blocked homotri- and homotetra-peptides from (αMe)Leu, a chiral Cα-methylated, γ-branched α-amino acid, have been prepared by solution methods and fully characterized. The molecular and crystal structures of pBrBz-[D-(αMe)Leu]3-OH monohydrate and pBrBz-[D-(αMe)-Leu]4-OBut(where pBrBz indicates p-bromobenzoyl) were determined by X-ray diffraction. The tripeptide carboxylic acid adopts a type-III β-turn conformation followed by an uncommon oxyanalogue of a type-III β-turn, the latter being stabilized by a 1â†�4 CO ⋯ H–O intramolecular H-bond. The three independent molecules in the asymmetric unit of the tetrapeptide ester are folded in a regular right-handed 310-helix. All (αMe)Leu residues exhibit φ, Ψ torsion angles in the helical region of the conformational map. These results indicate that: (i) the (αMe)Leu residue is an effective β-turn and helix promoter and (ii) the relationship between (αMe)Leu chirality and turn and helix handedness is the same as that shown by the γ-branched (αMe)Phe residue, but it is opposite to that characteristic of isovaline (Iva), with a linear side chain, the β-branched (αMe)Val residue and protein amino acids (including Leu).

Backbone modified formyl-methionyl tripeptide chemoattractants

Abstract The conformationally restricted tripeptides HCO-L-Met-L-Phe-OMe [where Xxx is L (D)-Iva, -(αMe)Val or -(αMe)Phe] were synthesized and tested for their β-glucosaminidase release activity. The [L-(αMe)Val] 2 - and [L-(αMe)Leu] 2 - analogues turned out to be the most active compounds examined. The positive effects induced by increasing side-chain hydrophobicity and by the L-chirality of the Xxx residue on peptide-receptor interactions are discussed.

Onset of the fully extended conformation in (αMe)Leu derivatives and short peptides

The X-ray diffraction crystal structures of the (αMe)Leu derivative mCIAc-d-(αMe)Leu-OH and the terminally protected tripeptide Z-d-(αMe)Leu-(l-Ala)2-OMe show the onset of the fully extended (C5) conformation for the (αMe)Leu residue in both independent molecules in the asymmetric unit of the former compound and in two out of the four independent molecules in the asymmetric unit of the latter compound. In addition, conformational analysis in CDCI3 solution (using FT-infra-red absorption and 1H nuclear magnetic resonance) revealed the occurrence of a significant population of fully extended conformers throughout the entire sequence of the (αMe)Leu homochiral homopeptides pBrBz-[d-(αMe)Leu]n-OtBu (from monomer to tetramer). Taken together, these results represent a clear indication that this peptide secondary structure, uncommon for protein amino acids and other Cα-methylated chiral residues, is not a rare observation in (αMe)Leu derivatives and short peptides.

Linear oligopeptides. Part 316. Conformational characterization of syndiotactic homo-peptides from Cα,α-disubstituted glycines

Terminally blocked, syndiotactic linear homo-peptides from Cα,α-disubstituted glycines Iva and (αMe)Val have been prepared to the hexapeptide and tripeptide amide levels, respectively, by solution methods and fully characterized. The molecular and crystal structures of pBrBz-(D-lva-L-lva)2-OBut methanol solvate, pBrBz-(D-lva-L-lva)2-D-lva-OBut methanol solvate, and Z-D-(αMe)Val-L-(aMe)Val-D-(aMe)Val-NHPri(pBrBz =p-bromobenzoyl, Z = benzyloxycarbonyl) were determined by X-ray diffraction. While the Iva pentapeptide and the (αMe) Val tripeptide amide are folded in an (incipient) left-handed 310-helical conformation, the Iva tetrapeptide adopts a double β-bend conformation of the II′–III type. The FTIR absorption and 1H NMR analyses support our contention that in chloroform solution, the longest syndiotactic homo-peptides may be folded in well developed 310-helical structures. This is the first structural study reported on regularly alternating (D–L) peptides based on conformationally constrained α-amino acids.

Linear oligopeptides. Part 329. Synthesis, characterization and solution conformational analysis of Cα-ethyl, Cα-benzylglycine[(αEt)Phe] containing peptides

For the first time a variety of derivatives and terminally blocked model peptides (to the pentapeptide level) of the sterically demanding (αEt)Phe residue have been synthesized (by solution methods) and fully characterized. The results of a solution conformational analysis, performed by using FTIR and 1H NMR spectroscopy, favour the conclusion that (αEt)Phe is a β-turn and helix promoter as strong as (αMe)Phe (Cα-methyl, Cα-benzylglycine) but more efficient than the Phe parent amino acid. In addition, a CD study of Nα-para-bromobenzoylated peptides suggests that the relationship between (αEt)Phe chirality and the screw sense of the turn and helical structures that are formed is the same as that found for (αMe)Phe peptides, i.e.L-amino acids give left-handed helicities. Interestingly, this relationship is opposite to that exhibited by protein amino acids, including Phe.

First unequivocal observation of the multiple fully extended conformation (25-helix) in a homopeptide from a Cα-methylated chiral α-amino acid

An X-ray diffraction analysis of pBrBz-[d-(αMe)Leu]3-OtBu revealed that in the crystal state this terminally blocked tripeptide adopts a multiple fully extended conformation (25-helix). This is the first unequivocal observation of such a structure in a homopeptide from a Cα-methylated chiral α-amino acid. No intermolecular NH. . . O=C H- bonds are seen in the crystal packing.

Crystal structure of oxazol-5(4H)-one from Nα-para-bromobenzoyl-Cα-methyl-D-leucyl-Cα-methyl-D-leucyl-Cα-methyl-D-leucine, C28H32BrN3O4

Source of material: see ref. 1. It crystallized from acetonitrile. The geometry of the heterocyclic ring is similar to that observed in other peptide-derived oxazol-5(4H)-ones (see ref. 2 and references therein). The backbone torsion angles about the Ν1-C8, C8-C14, and N2-C15 bonds are 51°, 44°, and 175°, respectively. The dihedral angle between normals to the average planes of the oxazolone and phenyl rings is 57°. Br1