Discovering protein secondary structures: classification and description of isolated alpha-turns.

Irregular protein secondary structures are believed to be important structural domains involved in molecular recognition processes between proteins, in interactions between peptide substrates and receptors, and in protein folding. In these respects tight turns are being studied in detail. They also represent template structures for the design of new molecules such as drugs, pesticides, or antigens.

Solvent-mediated conformational transition in beta-alanine containing cyclic peptides. VIII.

In the present paper we describe the solution nmr structural analysis and restrained molecular dynamic simulation of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-beta-Ala-beta-Ala). The conformational analysis carried out in CD3CN and dimethylsulfoxide (DMSO) solutions by nmr spectroscopy was based on interproton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. A restrained molecular dynamic simulation in vacuo was also performed to build refined molecular models.

Unusual conformational preferences of beta-alanine containing cyclic peptides. VII.

In the present paper we describe the synthesis, purification, and single crystal x-ray analysis of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-beta-Ala-beta-Ala). This compound crystallizes in the orthorhombic space group P2I2I2I from methanol and adopts in the solid state an unusual conformation characterized by a cis beta-Ala5-Pro1 peptide bond and by an intramolecular hydrogen bond stabilizing a C11-and a C12-ring structure. The C11 structure contains the Phe3 and the beta-Ala4 at the corner position of the turn; it is the first observation of a type II beta-turn enlargement due to the insertion of an extra methylene group of the beta-alanine residue.

Synthesis and structural characterization of 6I,6II-diamino-6I,6II-dideoxy-cyclomaltoheptaose, a difunctionalized beta-cyclodextrin.

6I,6II-Diamino-6I,6II-dideoxy-cyclomaltoheptaose was prepared using the regioselective procedure described by Tabushi. The difunctionalized beta-cyclodextrin crystallizes as hexadecahydrate in the orthorhombic space group P2(1)2(1)2(1), with a = 11.395(3), b = 32.

Preferred conformation of peptides rich in Ac8c, a medium-ring alicyclic C (alpha,alpha)-disubstituted glycine.

A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C (alpha,alpha)-disubstituted glycine 1-aminocyclooctane-1-carboxylic acid (Ac8c), and two Ala/Ac8c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 1H-NMR. The molecular structures of the amino acid derivative Z-Ac8c-OH, the dipeptide pBrBz-(Ac8c)2-OH and the tripeptide pBrBz-(Ac8c)3-OtBu were assessed in the crystal state by X-ray diffraction.

Bicyclic peptides as type I/type II beta-turn scaffolds.

We recently reported the rational design, synthetics, and structural characterization of the most potent and selective peptide-based neurokinin A antagonist thus far described: cyclo(Met1-Asp2-Trp3-Phe4-Dap5-Leu6)cyclo(2 beta-5 beta). Its bicyclic structure is characterized by a type I and a type II two beta-turn around Trp3-Phe4 and Leu6-Met1, respectively. In order to understand whether the two different beta-turned structures are determined by the bicyclic structure or by the amino acid type at the corner positions, we have synthesized the pseudo-symmetrical analogue cyclo(Phe1-Asp2-Trp3-Phe4-Dap5-Trp6)cyclo(2 beta-5 beta).

Solution and solid state structure of an aib-containing cyclodecapeptide inhibiting the cholate uptake in hepatocytes.

The conformational analysis of synthetic cyclodecapeptide c(Pro-Phe-phe-Aib-Leu)2 related to the cyclolinopeptide A, in the solid state and solution, has been carried out by x-ray diffraction and nmr spectroscopy. The structure of the monoclinic form obtained from methanol [a = 11.351 (5) A, b = 27.

Inversion of 3(10)-helix screw sense in a (D-alpha Me)Leu homo-tetrapeptide induced by a guest D-(alpha Me)Val residue.

The terminally blocked tetrapeptide pBrBz-[D-(alpha Me)Leu]2-D-(alpha Me)Val-D-(alpha Me)Leu-OfBu is folded in the crystal state in a left-handed 3(10)-helical structure stabilized by two consecutive 1<--4 C = O...

Bioactive peptides: conformational studies of [Tyr4] cyclolinopeptide A.

The solid state conformational analysis of [Tyr4] cyclolinopeptide A has been carried out by x-ray diffraction studies. The crystal structure of the monoclinic form, grown from a dioxane-water mixture [alpha = 9.849 (5) A, b = 20.

Conformational studies of heterochiral peptides with diastereoisomeric residues: crystal and molecular structures of linear dipeptides derived from leucine, isoleucine, and allo-isoleucine.

The x-ray diffraction analyses of three N- and C-terminally blocked L,D dipeptides, namely t-Boc-D-Leu-L-Leu-OMe (1), t-Boc-L-Ile-D-aIle-OMe (2), and t-Boc-D-aIle-L-Ile-OMe (3) containing enantiomeric or diastereomeric amino acid residues have been carried out. The structures were determined by direct methods and refined anisotropically to final Rf actors of 0.077, 0.

Conformational behaviour of a cyclolinopeptide A analogue: two-dimensional NMR study of cyclo(Pro1-Pro-Phe-Phe-Ac6c-Ile-ala-Val8).

The cyclic octapeptide cyclo[-Pro1-Pro-Phe-Phe-Ac6c-Ile-ala-Val8-] [C8-Ac6c], containing the Pro1-Pro-Phe-Phe sequence, followed by a bulky helicogenic C alpha,alpha-dialkylated glycine residue Ac6c [1-aminocyclohexane-1-carboxylic acid), and a D-Ala residue at position 7 has been synthesized. This cyclic peptide is a deletion analogue of the naturally occurring cyclic nonapeptide cyclolinopeptide A (CLA). It has been designed with the aim of studying the role that the Ac6c and D-Ala residues play on the conformational behaviour of the whole molecule and their influence on the conformation of the Pro1-Pro-Phe-Phe sequence when compared with cyclolinopeptide A.

The polypeptide 3(10)-helix as a template for molecular recognition studies. Structural characterization of a side-chain functionalized octapeptide.

A N alpha-blocked, Aib-rich octapeptide methylamide containing two N omega-benzoylated L-Lys residues at positions 3 and 6 was synthesized by solution methods and fully characterized. A solution and crystal-state conformational analysis, performed by using FT-IR, 1H NMR, CD, and X-ray diffraction techniques, showed that the peptide is folded into a regular, right-handed 3(10)-helix stabilized by seven consecutive N-H..

Specific interaction between cyclophilin and cyclic peptides.

Cyclophilin A, a peptidyl-prolyl cis-trans is isomerase that catalyzes the otherwise slow isomerization of Xaa-Pro imidic bond, specifically binds the immunosuppressant cyclosporin A. Herein we report evidence on binding of cyclolinopeptide A and its synthetic analogue, [Aib5,6-D-Ala8]cyclolinopeptide, to bovine cyclophilin A. Binding experiments were monitored by fluorescence, CD, and second-derivative spectroscopies, evidencing no remarkable rearrangement of protein structure organization.

Conformational studies on synthetic peptides reproducing the dibasic processing site of pro-ocytocin-neurophysin.

Synthetic peptides reproducing the proteolytic processing site of pro-ocytocin were studied by different spectroscopic techniques, including circular dichroism, Fourier transform infrared absorption, and mono and bidimensional nuclear magnetic resonance, in order to ascertain the possible role of three-dimensional structure in the recognition process by maturation enzymes. Experimental results were compared with energy minimization calculations and suggest that: (i) the region situated on the N-terminus of the Lys-Arg doublet may form a beta-turn; (ii) the sequential organization of the residues participating in the beta-turn determines the privileged relative orientation of the basic amino acid sidechains and the subtype of turn; and (iii) the peptide segment situated on the C-terminal side of the dibasic doublet may assume a helix arrangement. These findings, in spite of the limitations connected to the flexibility of linear peptides, seem to substantiate the hypothesis that structural motifs around the cleavage site could be important for recognition and processing.

[Aib5,6-D-Ala8]-cyclolinopeptide A, grown from a benzene/acetonitrile mixture.

cyclo-(Prolyl-prolyl-phenylalanyl-phenylalanyl- alpha-aminoisobutyryl-alpha-aminoisobutyryl-isoleucyl-D-alan yl-valyl) ([Aib5,6-D-Ala8]-cyclolinopeptide A), grown from benzene/acetonitrile mixture, crystallizes with one acetonitrile and two water molecules. The molecular structure is almost identical to that obtained from methanol/water. The dimension of the solvent channels found in these structures is reduced in the present one, but the intramolecular hydrogen-bond pattern is preserved.

Mixed conformation in C alpha, alpha-disubstituted tripeptides: x-ray crystal structures of Z-Aib-Dph-Gly-OMe and Bz-Dph-Dph-Gly-OMe.

We report here the synthesis and molecular structure in the solid state of fully protected tripeptides containing C alpha, alpha-diphenylglycine (Dph), namely Z-Aib-Dph-Gly-OMe (Aib: C alpha, alpha-dimethylglycine) and Bz-Dph-Dph-Gly-OMe. The molecular conformation around the Dph residue, containing two bulky substituents, is fully extended, while the Aib residue, containing two smaller groups on the C alpha atom, adopts the typical 3(10)/alpha-helical conformation. Gly residues, without substituents on the C alpha atom, show different conformational preferences.

Beta-alanine containing cyclic peptides with turned structure: the "pseudo type II beta-turn." VI.

In the present paper we describe the synthesis, purification, single crystal x-ray analysis, and nmr solution characterization, combined with restrained molecular dynamic simulations, of the cyclic hexapeptide cyclo-(L-Pro-L-Phe-beta-Ala)2. The peptide was synthesized by classical solution methods and the cyclization of the free hexapeptide was accomplished in good yields in diluted methylene chloride solution using N,N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P2(1) from methanol-dichloromethane solution.

Beta-alanine containing cyclic peptides with predetermined turned structure. V.

In the present paper we describe the synthesis, purification, single crystal x-ray analysis, and solution structural characterization by nmr spectroscopy, combined with restrained molecular dynamic simulations, of the cyclic hexapeptide cyclo-(Pro-Phe-beta-Ala-Phe-Phe-beta-Ala). The peptide was synthesized by classical solution methods and the cyclization of the free hexapeptide was accomplished in good yields in diluted methylenechloride solution using N,N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P2(1) from methanol/ethyl acetate.

A crystal structure with features of an antiparallel alpha-pleated sheet.

A single-crystal x-ray diffraction analysis of Boc-L-Ala-D-aIle-L-Ile-OMe has been carried out. The analysis has shown (a) that the tripeptide molecules have in part an alpha-extended conformation, the torsion angles of the L-Ala and D-aIle residues being psi 1 = -75.1 degrees and psi 1 = -25.

Defect peptide chemistry: perturbations in the structure of a homopentapeptide induced by a guest residue interrupting side-chain regularity.

The fully blocked pentapeptide Tfa-(Deg)2-L-Abu-(Deg)2-OtBu (Tfa: triflouroacetyl; Deg: C alpha, alpha-diethylglycine; Otbu: tert-butoxy) adopts in the crystal state a regular, right-handed 3(10)-helical structure stabilized by three N--H...

A second polymorph of a helical decapeptide.

A crystal-state structural analysis of the terminally blocked apolar decapeptide pBrBz-(Aib-L-Ala)5-OMe bis-dimethylsulfoxide solvate was performed by x-ray diffraction. The peptide molecules are basically alpha-helical with five 1<--5 C = O..

Bioactive peptides: solid state, solution and molecular dynamics studies of a cyclolinopeptide A-related cystinyl cyclopentapeptide.

The conformational analysis of [sequence: see text] the disulphide cyclopeptide-related cyclolinopeptide A, has been carried out by solid state methods using x-ray diffraction techniques, in solution by nmr, CD, ir spectroscopies, and by molecular dynamics (MD) analysis. The structure of the monoclinic form, obtained from ethanol (a = 11.303(2) A, b = 14.

Conformational versatility of the N alpha-acylated tripeptide amide tail of oxytocin. Synthesis and crystallographic characterization of three C2 alpha-backbone modified, conformationally restricted analogues.

The synthesis, physical and analytical characterization, and crystal-state structural analysis by X-ray diffraction of three analogues of the N alpha-acylated tripeptide amide tail of oxytocin, each containing a cyclic C alpha, alpha-disubstituted glycine at position 2, have been performed. The peptides are Boc-L-Pro-Ac3c-Gly-NH2, Z-L-Pro-Ac5c-Gly-NH2 and Z-L-Pro-Ac6c-Gly-NH2. While the former is folded in a type-II beta-turn conformation at the -L-Pro-Ac3c- sequence, the two latter tripeptides form two consecutive (type-II, type-I') beta-turns.

[Pulmonary hamartoma].

Pulmonary hamartoma is a rare benign tumor often found by chance. Only in 10% of cases are some calcifications like "pop corn". Fibrobroncho-scopy is help only in endobronchial forms; they don't reach 10% of cases.