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An example of a solvent-driven [alpha]/[3.sub.10]-helix dimorphismis described for a peptide molecule in the crystalline state. The studies have shown that the interconversion between [alpha]- and [3.sub.10]-helices might be allowed even in peptides composed by [C.sup.[alpha]]-tetrasubstituted [alpha]-amino acids and has provided clues for understanding the interactions of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) with helical peptides.

An effective and flexible computational approach is described and its usefulness and reliability is demonstrated by the tuning of the equilibrium between [3.sub.10] and [alpha]-helices of polypeptides by different solvents. The generality of this computational strategy and its applicability in effective and user-friendly computer codes have paved the way toward applications in the field of biomolecules and other complex systems.

Suppression of diagonal peaks by controlling polarizations of infrared pulses reveals cross-peak patterns that are crucial for structural determination. A doublet feature is observed when the peptide ester forms a 3(sub 10-) helix in CDCI(sub 3) and trifluoroethanol and when it is at the initial stage of 3(sub 10-) to an alpha-helix transition in 1,1,1,3,3,3-hexafluoro-2-propanol.

Monodisperse hexapeptides having lipoic acid coupled to the N-terminus were self-assembled on gold substrates. X-ray photoelectron spectroscopy (XPS), angle dependent XPS, and grazing angle Fourier transfer infrared reflection-absorption spectroscopy (FTIR-RAS) were used to investigate the self-assembled monolayer (SAM) film compositions.

In the dipeptides Boc-Bip-L-Val-OMe and Boc-Bip-D-Val-OMe, and induced axial chiralityh in the biphenyl core of the Bip residue, a conformationally labile, proatropoisomeric C(super alpha, alpha)-disubstituted glycine, is observed by electronic CD and 1H NMR. The findings show that the chiral induction is significantly higher when the Val residue is located at the C-terminal position of Bip.

A set of analogues and dipeptide amides characterized by chiral C(super alpha)-tetrasubstituted alpha-amino acids of varied bulkiness and optical configurations are examined. Results confirm the close relationship between the beta-hairpin 3D-structure and the catalytic activity of the peptides.

Research into the electron transfer to peresters in N,N-dimethylformamide is presented. It was found that, irrespective of the way in which the reaction is undertaken, electron transfer to the perester acceptor is an extremely slow donor electron transfer.

A lipophilic alpha/310-helical, c alpha-methylated peptide was studied with regard to folding of membrane proteins.

Research was conducted to examine the electron spin resonance of single and double TOAC-labeled trichogin GA IV analogues where TOAC is a rigid nitroxide amino acid and acts as an Aib analogue. The objectives are to determine the conformations of trichogin GA IV in methanol solution and to extend double label electron spin resonance by using half-field transitions. Results reveal trichogin GA IV conformations that were not previously seen by either nuclear magnetic resonance spectroscopy or crystallography.

Research was conducted to examine the solvent-dependent intramolecular electron transfer in a peptide-linked (Ru(bpy)3)2+-C60 dyad. The electron transfer in chlorinated hydrocarbons was observed to cause quenching of the emission related to the ruthenium metal-to-ligand charge-transfer excited state. Results reveal that the solvent-dependent conformational changes of a peptide bridge affect the electron-transfer process that takes place in the (Ru(bpy)3)2+/C60 dyad.

Research was conducted to examine the synthesis of the first homopeptide series, pBrBz-(Delta-ala)n-OMe (n = 1-6) based on a C-alpha, beta-didehydro-alpha-amino acid using solution methods. The objective was to determine the preferred conformation of the residue by employing 1H NMR and FTIR absorption techniques in solution while using X-ray diffraction in the crystal state. Results emphasize the need for carefully taking into consideration C-beta-substitution in Delta-AAs for a correct peptide design.

The conformational preferences of a novel C(alpha)-tetrasubstituted alpha-amino acid characterized by concomitant Ci(alpha) - Ci(alpha) cyclization and the presence of two ether oxygen atoms in the gamma-positions of the six-membered ring 1,3-dioxane system were investigated. The homooligopeptide series based on O,O-isopropylidene-alpha-hydroxymethylserine from dimer through pentamer was synthesized. It was found that the extent of regular 3(10)-helix formation in peptides increases as peptide main-chain length increases.

A spectroscopic investigation was undertaken to ascertain whether the ordered structure of short linear peptides' crystal state is preserved in solution. The conformational equilibria characterizing the peptides containing tryptophan (Trp) and the nitroxide derivative, Toac, was due to the rotation of the dihedral angles of the Trp side chain. Results indicate that irrespective of the polarity of the solvents used, the peptides examined maintain the basic features of the crystal state, and exhibit poor flexibility in solution.

The conformationally restricted, N-blocked heptapeptide methylamide mBrBz-[L-Iva-L-(alphaMe)Val]2-L-(alphaMe)Phe-L-(alphaMe)Val-L-Iva-NHMe was fully characterized and synthesized by solution methods. A single crystal was grown and the x-ray diffraction structure of its synthetic precursor, the Nalpha-benzyloxycarbonylated analogue, was solved. Both peptide molecules are folded in the crystal state into a fully developed, regular right-handed 3(sub10-)helical conformation.

Vibrational and electronic circular dichroism (VCD and ECD), and Fourier transform infrared (FTIR) spectra of the homo-oligopeptide series Z-(L-(alphaMe)Val)(sub n)-OtBu (n = 3-8) and selected Ac-(L-(alphaMe)Val)(sub n)-OtBu oligomers (n = 4,6,8) were obtained. The ECD and FTIR findings for the octamer demonstrated a concentration-dependent solution structure, which at higher concentrations is 3(sub 10)-helical and interacting. For these peptides, the N(super alpha)-blocking group seems to have only little effect on the resultant ECD and practically no effect on the VCD spectra.

A fulleropyrrolidine derivative is produced through the thermal ring opening of N-(3-(triethoxysilyl)propyl)-2-carbomethoxyaziridine in the presence of Csub60. The derivative is covalently attached to HPLC silica gel, and can be used to examine binding affinities of potential hosts for immobilized Csub60. High size slectivities were obtained for cyclic oligomeric compounds.

The structures of the 2-alkoxy-5(4H)-oxazolones derived from 2,2,6,6-tetramethyl-4-((benzyloxycarbonyl)amino)-1-oxypiperidine-4-carboxyli c acid and 2,2,6,6-tetramethyl-4-((9'-fluorenylmethoxycarbonyl)amino)-1-oxypiperidine-4 -carboxylic acid were solved by single-crystal X-ray diffraction. These two structures represent the first examples of 2-alkoxy-5(4H)-oxazolones in the crystal state. The computed geometries of the 2-alkoxy- and 2-alkyl-5(4H)-oxazolone systems at the MP2/6-31+G(d,p) level conformed with those experimentally determined in the crystal state.

The unprecedented, unnatural alpha-amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) is used to examine the structure of hexameric sequences. It allows the study of Ala-rich peptides containing C(alpha)-tetrasubstituted residues without worrying over signal overlap that frequently hinders nuclear magnetic resonance investigations. C(alpha)-tetrasubstituted amino acids were found to prefer the helix, but do not 'lock in' the helical conformation.

Derivatives and peptides of the new alpha-amino acid 3,4 fulleroproline are synthesized by means of 1,3-dipolar cycloadditions of azomethine ylides to C60. They are separated into optically pure enantiomers via enantioselective high-performance liquid chromatography or silica column separation. Their configurational assignments are confirmed by quantum mechanical calculations.

The facile synthesis of fullerenes, based on peptides which are optically and chemically pure, is discussed. A peptide filled with Aib is subjected to experimental studies due to their involvement in molecular identification examinations as templates. These peptides are restrained on the basis of their structure. These compounds can be successfully exposed to X-ray diffraction studies due to their high attraction for crystallization. All peptides which are soluble in water and display high levels of biological metabolism can be subjected to these experiments.

The oxidation of some tripeptide esters protected at the N-terminus with carbamate or amide groups is achieved under mild conditions with no loss of configuration at the chiral centers by using methyl(trifluoromethyl)dioxirane (TFDO). Nitro derivatives are formed due to oxidative deprotection of the carbamate group with excess dioxirane and a rationale is proposed for describing the dependence of the selectivity upon the nature of the protecting group.

A combination of two-dimensional infrared (2D IR) spectroscopy and isotope editing of amide-I and amide-II modes is used for probing the vibrational coupling between hydrogen-bonded peptide linkages in a [3.sub.10]-helix. The isotope-dependent cross-peaks have provided important information on local structure like the formation of a single helix turn, which is vital for studying protein folding process.

The time-resolved femtosecond spectroscopy in conjunction with nonequilibrium molecular dynamics (MD) simulations was used to study the energy transport in a short helical peptide in chloroform solution. A simple harmonic model of heat transport adopted on the bases of results showed that the heat diffusivity decreased significantly at temperatures initially reached by high-energy excitation.

The onset of the [3.sub.10]-helical secondary structure and the evolution of two-dimensional infrared (2D IR) spectral patterns in the Aib oligopeptides is studied. The onset of the helical structure is shown to occur at the pentapeptide level.

The central-to-axial induction of chriality from the C-terminal [[beta].sup.3]-Xaa*-OMe ([[beta].sup.3]-HAla, [[beta].sup.3]-HVal, [[beta].sup.3]-HLeu, [[beta].sup.3]-HPro) or cyclic [beta]-Xaa*-OMe (ACHC, ACPC) amino ester residues to the [N.sup.[alpha]]-Boc protected, pro-atopoisomeric, [C.sup.[alpha]]-tetrasubstituted [alpha]-amino acid Bip is shown in simple linear dipeptides. The results have shown that MeOH is the best solvent for the application of the Bip method to [alpha]- or [beta]-amino acid configurational issues.

A minimal ring-closing metathesis reaction (RCM) constraint for the [3.sub.10]-helix is developed, which is a relatively common structural motif in proteins and peptides containing [C.sup.[alpha]]-tetrasubstituted [alpha]-amino acids. It is shown that a minimal, RCM-derived, macrocyclic constraint can be incorporated into [3.sub.10]-helical peptides.

The two-dimensional infrared (2D- IR) spectra of [C.sub.alpha]-alkylated model octapeptides Z-[(Aib).sub.8]-OtBu, Z-[(Aib).sub.5]-L-Leu-[(Aib).sub.2]-OMe and Z-[[L-([alpha]MeVal)].sub.8]-OtBu in the amide I region is evaluated to determine the 2D spectral signatures features of [3.sub.10-] and [alpha]-helical conformations. The sensitivity of cross-peak trends to various helical conformations and the dependence of chain lengths of the special characteristics for short [3.sub.10-] and alpha-helices are described.

An ab initio integrated computational approach is applied to evaluate the interpretation of the continuous wave electron spin resonance (CW-ESR) spectra of the double-spin labeled, [3.sub.10]-helical, peptide Fmoc-[(Aib-Aib-TOAC).sub.2]-Aib-OMe dissolved in acetonitrile. It is suggested that combination of sensitive ESR spectroscopy and sophisticated modeling can provide three-dimensional (3D) structural and dynamic information on molecular systems.

A comparative study on two synthetic analogues of the natural peptide trichogin GA IV is conducted to investigate the effect of lipidation on the membrane perturbing activity of peptaibol antibiotics. It is found that both analogues are labeled with a hydrophobic fluorescent probe, but one of them lacked the N-terminal n-octanoyl chain, present in the natural peptide.

The photophysical and conformation properties of the three analogues F0T1, F0T4, and F0T8 are reported along with the dynamics through which F0T8 collapses from an elongated helix to a compact three-dimensional (3D) arrangement of the helix-turn-helix type. The results reveal a transition from an elongated, helical conformation to a family of compact, folded structures mimicking a helix-turn-helix motif, which might represent a model of the early steps of the protein hydrophobic collapse.

The synthesis, characterization, and properties of a series of gold nanoclusters protected by thiolated peptides based on the alpha-aminoisobutyric acid (Aib) unit are described. The infrared (IR) and NMR spectra has shown that in the monolayer the peptides are involved in both intra- and interligand C=O...H-N hydrogen bonds.

Unambiguous proofs that the screw sense of peptide turns and helices may be dictated not only by the amino acid asymmetric alpha-carbons but by the topological properties of their side-chain beta-carbons as well are reported. The peptides based on c3diPhe studied are related to those formed by the binaphthyl alpha-amino acid, in the sense that both residues lack an asymmetric center in the main chain.

A series of donor-spacer-acceptor (D-Sp-A) systems are devised and synthesized to study the relationship between rate and driving force of intramolecular dissociative electron transfers. The electrochemical analysis provided clear evidence of a concerted dissociative electron-transfer mechanism, leading to the cleavage of the O-O bond.

The electron transfer (ET) might occur by an incoherent hopping mechanism where the bridge is more directly involved in the process. This mechanism requires a thermally activated endergonic charge injection from donor (D) to the directly connected bridge unit.

The peptide backbone is essential in assisting long-range electron transfer (ET) in proteins. The main ingredient that contributed to showing the important effect of the intramolecular H-bonds on the ET rate is the propensity of Aib peptides to form a well-defined and rigid structure, a property that is maintained even in aqueous solution.

The concomitant occurrence of peptide 310 and alpha helices was probed by NMR.

Research was conducted to examine a bimetallic helical heptapeptide as a transphosphorylation catalyst in water. The peptide comprises five copies of the C-alpha-tetrasubstituted alpha-aminoisobutyric acid with the assumption that it would be able to induce a stable helical conformation even to such a very short sequence. Results demonstrate that very short, easily accessible, economically synthesized and rationally designed peptide sequences may provide the appropriate scaffold for the realization of effective catalysts by regulating their secondary structure.

The electronic circular dichroism (CD) spectra of a right-handed 3(10)-helical peptide were observed. Specifically, three L-(alpha-Me)Val (sub 8) homopeptide tert-butyl esters containing acetyl, benzyloxy-carbonyl and p-bromobenzoyl N(alpha)-blocking groups were prepared and spectroscopically characterized in three solvents. The results, which were consistent with theoretical predictions, revealed a negative CD band at 207 nm.