Synthetic α-helical peptides incorporating intercalators for DNA recognition

The design and synthesis of a water-soluble 14-residue peptide, in which a quinoline intercalator is attached to the peptide backbone via alkylation of a central cysteine residue, is reported. 600 MHz ¹H NMR spectroscopy and circular dichroism indicate that the peptide forms a nascent helix in aqueous solution, ie. an ensemble of turn-like structures over several adjacent residues in the peptide. A large number of sequential d_NN(i, i+1) connectivities were observed in NOESY spectra, and titration of trifluoroethanol into a solution of the peptide resulted in the characteristic CD spectrum expected for an α-helix. At low DNA concentrations, CD spectroscopy indicates that this helical conformation is stabilized, presumably due to folding of the peptide in the major groove of DNA.     

β-Turn conformations in crystal structures of model peptides containing α,α-Di-n-propylglycine and α,α-Di-n-butylglycine

The crystal state conformations of three peptides containing the α,α-dialkylated residues. α,α-di-n-propylglycine (Dpg) and α,α-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Alu-OMe (I) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II β-turn conformations with Ala (1) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: ? = 66.2°, ψ = 19.3°; III: ? = 66.5°. ψ = 21.1°) deviate appreciably from ideal values for the i + 2 residue in a type II β-turn. In both peptides the observed (N…O) distances between the Boc CO and Ala (3) NH groups are far too long (1: 3.44 Å: III: 3.63 Å) for an intramolecular 4 → 1 hydrogen bond. Boc-Ala-Dpg-Ata-NHMe (II) crystallizes with two independent molecules in the asymmetric unit. Both molecules HA and HB adopt consecutive β-turn (type III-III in HA and type III-I in IIB) or incipient 3₁₀-helical structures, stabilized by two intramolecular 4 → 1 hydrogen bonds. In all four molecules the bond angle N-C^α-C′ (τ) at the Dxg residues are ≥ 110°. The observation of conformational angles in the helical region of ?,ψ space at these residues is consistent with theoretical predictions. © 1995 John Wiley & Sons, Inc.     

Cyclic strain induces reorganization of integrin α5β1 and α2β1 in human umbilical vein endothelial cells

Cyclic strain has been shown to modulate endothelial cell (EC) morphology, proliferation, and function. We have recently reported that the focal adhesion proteins focal adhesion kinase (pp125^FAK) and paxillin, are tyrosine phosphorylated in EC exposed to strain and these events regulate the morphological change and migration induced by cyclic strain. Integrins are also localized on focal adhesion sites and have been reported to induce tyrosine phosphorylation of pp125^FAK under a variety of stimuli. To study the involvement of different integrins in signaling induced by cyclic strain, we first observed the redistribution of α and β integrins in EC subjected to 4 h cyclic strain. Human umbilical vein endothelial cells (HUVEC) seeded on either fibronectin or collagen surfaces were subjected to 10% average strain at a frequency 60 cycles/min. Confocal microscopy revealed that β₁ integrin reorganized in a linear pattern parallel with the long axis of the elongated cells creating a fusion of focal adhesion plaques in EC plated on either fibronectin (a ligand for α₅β₁) or collagen (a ligand for α₂β₁) coated plates after 4 h exposure to cyclic strain. β₃ integrin, which is a vitronectin receptor, did not redistribute in EC exposed to cyclic strain. Cyclic strain also led to a reorganization of α₅ and α₂ integrins in a linear pattern in HUVEC seeded on fibronectin or collagen, respectively. The expression of integrins α₅, α₂, and β₁ did not change even after 24 h exposure to strain when assessed by immunoprecipitation of these integrins. Cyclic strain-induced tyrosine phosphorylation of pp125^FAK occurred concomitant with the reorganization of β₁ integrin. We concluded that α₅β₁ and α₂β₁ integrins play an important role in transducing mechanical stimuli into intracellular signals. J. Cell. Biochem. 64:505–513. © 1997 Wiley-Liss, Inc.     

Folding type-specific secondary structure propensities of amino acids,derived from α-helical, β-sheet, α/β, and α+β proteins of known structures

Folding type-specific secondary structure propensities of 20 naturally occurring amino acids have been derived from α-helical, β-sheet, α/β, and α+β proteins of known structures. These data show that each residue type of amino acids has intrinsic propensities in different regions of secondary structures for different folding types of proteins. Each of the folding types shows markedly different rank ordering, indicating folding type-specific effects on the secondary structure propensities of amino acids. Rigorous statistical tests have been made to validate the folding type-specific effects. It should be noted that α and β proteins have relatively small α-helices and β-strands forming propensities respectively compared with those of α+β and α/β proteins. This may suggest that, with more complex architectures than α and β proteins, α+β and α/β proteins require larger propensities to distinguish from interacting α-helices and β-strands. Our finding of folding type-specific secondary structure propensities suggests that sequence space accessible to each folding type may have differing features. Differing sequence space features might be constrained by topological requirement for each of the folding types. Almost all strong β-sheet forming residues are hydrophobic in character regardless of folding types, thus suggesting the hydrophobicities of side chains as a key determinant of β-sheet structures. In contrast, conformational entropy of side chains is a major determinant of the helical propensities of amino acids, although other interactions such as hydrophobicities and charged interactions cannot be neglected. These results will be helpful to protein design, class-based secondary structure prediction, and protein folding. © 1998 John Wiley & Sons, Inc. Biopoly 45: 35–49, 1998     

Circular dichroism studies of α-aminoisobutyric acid-containing peptides: Chain length and solvent effects in alternating Aib-L-Ala and Aib-L-Val sequences

The CD spectra of the peptides Boc-X-(Aib-X)_n-OMe (n = 1, 2, 3) and Boc-(Aib-X)₅-OMe, where X = L -Ala or L -Val have been examined in several solvents. The X = Ala and Val peptides behave similarly in all solvents, suggesting that the Aib residues dominate the folding preferences of these peptides. The decapeptides adopt helical conformations in methanol and trifluoroethanol, with characteristic negative CD bands at 222 and 205 nm. In the heptapeptides, similar spectra with reduced intensities are observed. Comparison with nmr studies suggest that estimates of helical content in oligopeptides by CD methods may lead to erroneous conclusions. The pentapeptides yield solvent-dependent spectra indicative of conformational perturbations. Peptide association in dioxane results in an unusual spectrum with a single negative band at 210 nm for the decapeptides. Disaggregation is induced by the addition of methanol or water to dioxane solutions. Aggregation of the heptapeptides is less pronounced in dioxane, suggesting that a critical helix length may be necessary to promote association stabilized by helix dipole–dipole interactions.     

Experimental chiroptical verification of linkage flexibility in methyl 3-O-(α-D-mannopyranosyl)-α-D-mannopyranoside

Vacuum UV CD spectra of methyl 3-O-(α-D -mannopyranosyl)-α-D -mannopyranoside in D₂O and as a cast film were obtained in the 145–200 nM region. The disaccharide solution CD per residue is nearly identical to that of the monosaccharide solution CD, and to the monosaccharide film CD. Conversely, the disaccharide film spectrum exhibits a strong positive CD linkage contribution in the 160–170 nm range, which is consistent with the known crystal conformation under the aegis of previously determined sector rules. The close similarity between the monosaccharide and disaccharide solution spectra, therefore, reflects conformational averaging in which the net linkage contribution is approximately zero. The present observation of significant solution linkage flexibility confirms previous conclusions based on optical rotation, as well as conclusions of others based on nmr data. Moreover, when combined with those earlier results, the present work demonstrates the population of at least three distinct potential energy wells on the disaccharide ϕ, ψ potential energy surface. © 1996 John Wiley & Sons, Inc.     

The use of spectral decomposition via the convex constraint algorithm in interpreting the CD-observed unfolding transitions of C coils

Decomposition of CD spectra for the unfolding of both coiled-coil and single-helical molecules is carried out via the convex constraint algorithm (CCA) [A. Perczel, M. Hollósi, G. Tusnády, and G. D. Fasman (1991) Protein Engineering, Vol. 4, pp. 669–679]. Examined are (1) our thermal unfolding data for rabbit αα-tropomyosin and chicken gizzard γγ- tropomyosin coiled coils, and for a35-residue, tropomyosin-model peptide that forms single helices, not coiled coils; (2) extent pH-induced unfolding data for 50- and 400-residue poly-L -glutamic acid. Each set of spectra shows a sharp isodichroic point near 203 nm. We find here that the CCA is of sharply limited use for analyzing such data. The component spectra obtained for a given substance not only depend on the particular experimental spectra included and on the chosen number of component spectra, but all pass through the experimental isodichroic point. The latter is physically unlikely for more than three component spectra, and physically impossible for conformers, such as β structures, having known isodichroic points elsewhere. Our conclusions are in contrast to those of an extant decomposition via CCA of thermal spectra for rabbit αα-tropomyosin [N. J. Greenfield and S. E. Hitchcock-DeGregori(1993) Protein Science, Vol. 2, pp. 1263-1273] that postulates the existence of five conformers, including β structures, in the unfolding. Moreover, an extant diagnostic based on the θ₂₂₂/θ₂₀₈ ratio and allegedly distinguishing between spectra for coiled coil and for single α-helix is shown here to be unreliable. © 1995 John Wiley & Sons, Inc.     

Design and synthesis of novel nonpolar host peptides for the determination of the 310- and α-helix compatibilities of α-amino acid buildig blocks: An assessment of α,α-disubstituted glycines

The present work describes three novel nonpolar host peptide sequences that provide a ready assessment of the 3₁₀- and α-helix compatibilities of natural and unnatural amino acids at different positions of small- to medium-size peptides. The unpolar peptides containing Ala, Aib, and a C-terminal p-iodoanilide group were designed in such a way that the peptides could be rapidly assembled in a modular fashion, were highly soluble in solvent mixtures of triflouroethanol and H₂O for CD- and two-dimensional (2D) nmr spectroscopic analyses, and showed excellent crystallinity suited for x-ray structure analysis. To validate our approach we synthesized 9-mer peptides 79a–96 (Table IV), 12-mer peptides 99–110c (Table V), and 10-mer peptides 120a–125d and 129–133 (Table VI and Scheme 8) incorporating a series of optically pure cyclic and open-chain (R)- and (S)-α,α-disubstituted glycines 1–10 (Figure 2). These amino acids are known to significantly modulate the conformations of small peptides. Based on x-ray structures of 9-mers 79a, 80, and 87 (Figures 4–7), 10-mers 124c, 131, and 132 (Figures 9–12), and 12-mer peptide 102b (Figure 13), CD spectra of all peptides recorded in acidic, neutral, and basic media and detailed 2D-nmr analyses of 9-mer peptide 86 and 12-mer 102b, several interesting conformational observations were made. Especially interesting results were obtained using the convex constraint CD analysis proposed by Fasman on 9-mer peptides 79a–d, 80, 81, 86, and 87, which allowed us to determine the relative content of 3₁₀- and α-helical conformations. These results were fully supported by the corresponding x-ray and 2D-nmr analyses. As a striking example we found that the (S)- and (R)-β-tetralin derived amino acids (R)- and (S)-1 show excellent α-helix stabilisation, more pronounced than Aib and Ala. These novel reference peptide sequences should help establish a scale for natural and unnatural amino acids concerning their intrinsic 3₁₀- and α-helix compatibilities at different positions of medium-sized peptides and thus improve our understanding in the folding processes of peptides. © 1997 John Wiley & Sons, Inc. Biopoly 42: 575–626, 1997     

Structural interpretation of the two-site binding of troponin on the muscle thin filament

Conditions are described for the quantitative removal of amino acid residues 274 to 284 from rabbit muscle α-tropomyosin with carboxypeptidase A. The product, non-polymerizable tropomyosin, has a much reduced affinity for the tropomyosinbinding fragment CB1 (residues 1 to 151) of troponin-T. Iodination of α-tropomyosin and non-polymerizable tropomyosin by ¹²⁵I and lactoperoxidase was carried out in the presence and absence of CB1. Following tryptic digestion and peptide mapping, the radioactivities of the labeled tyrosine peptides were compared. In the presence of CB1, tyrosine residues 261 and 267 were iodinated only to the extent of 30 to 40% as compared with the same tyrosine residues in the absence of CB1, All other tyrosine residues (60, 162, 214 and 221) were iodinated to a similar level in the absence or presence of CB1. With non-polymerizable tropomyosin, the presence of CB1 had a much reduced effect on the level of labeling of the tyrosine residues. We conclude that the highly helical region of troponin-T (residues 71 to 151) binds close to or at the COOH-terminal end of the tropomyosin molecule. Taken together with other considerations and recent observations, the results can be interpreted in terms of the two-site model for troponin attachment to the thin filament. A calcium-insensitive site would involve interaction of the highly helical CB2 region of troponin-T (residues 71 to 151) and the COOH-terminal region of tropomyosin (residues 258 to 284) and perhaps the NH₂-terminal overlap region (residues 1 to 9). A calcium-sensitive site would involve the interaction of troponin-T in the neighborhood of cysteine 190 of tropomyosin in F-actin-tropomyosin assemblies both directly and indirectly through the association of its COOH and NH₂-terminal regions with the troponin-I and C components.     

Kinetic steps for α-helix formation

The kinetics of α-helix formation in polyalanine and polyglycine eicosamers (20-mers) were examined using torsional-coordinate molecular dynamics (MD). Of one hundred fifty-five MD experiments on extended (Ala)₂₀ carried out for 0.5 ns each, 129 (83%) formed a persistent α-helix. In contrast, the extended state of (Gly)₂₀ only formed a right-handed α-helix in two of the 20 MD experiments (10%), and these helices were not as long or as persistent as those of polyalanine. These simulations show helix formation to be a competition between the rates of (a) forming local hydrogen bonds (i.e. hydrogen bonds between any residue i and its i + 2, i + 3, i + 4, or i + 5th neighbor) and (b) forming nonlocal hydrogen bonds (HBs) between residues widely separated in sequence. Local HBs grow rapidly into an α-helix; but nonlocal HBs usually retard helix formation by “trapping” the polymer in irregular, “balled-up” structures. Most trajectories formed some nonlocal HBs, sometimes as many as eight. But, for (Ala)₂₀, most of these eventually rearranged to form local HBs that lead to α-helices. A simple kinetic model describes the rate of converting nonlocal HBs into α-helices. Torsional-coordinate MD speeds folding by eliminating bond and angle degrees of freedom and reducing dynamical friction. Thus, the observed 210 ps half-life for helix formation is likely to be a lower bound on the real rate. However, we believe the sequential steps observed here mirror those of real systems. Proteins 33:343–357, 1998. © 1998 Wiley-Liss, Inc.     

The effects of stabilizing mutations in the central part of the α-chain of tropomyosin on the structural and functional properties of αβ-tropomyosin heterodimers

The effects of the D137L/G126R double mutation in the central part of the tropomyosin α-chain via the simultaneous replacement of two highly conserved non-canonical residues, viz., Asp137 and Gly126, by canonical residues Leu and Arg, respectively, on the properties of the αβ-tropomyosin heterodimer have been studied. It has been shown using circular dichroism that this mutation substantially increases the thermal stability of αβ-tropomyosin heterodimers, which, nevertheless, remains lower than that of αα-tropomyosin homodimers with these mutations in both α-chains. The stability of tropomyosin complexes with F-actin has also been studied by measuring the temperature dependences of their dissociation, which is detected by a decrease in light scattering. It has been revealed that αβ-tropomyosin heterodimers carrying the D137L/G126R mutation in the α-chain dissociate from the surface of actin filaments at a higher temperature than ββ-homodimers but at a lower temperature than αα-homodimers with these mutations in both α-chains. It has also been shown using the in vitro motility assay that D137L/G126R substitution in the α-chain increases the sliding velocity of regulated actin filaments in the case of αα-homodimers, while it noticeably decreases the velocity in the case of αβ-tropomyosin heterodimers. Thus, we can conclude that mutations in one of the chains of the tropomyosin dimeric molecule may have different effects on the properties of tropomyosin homodimers and heterodimers.     

Engineered cystine knot peptides that bind αvβ3, αvβ5, and α5β1 integrins with low‐nanomolar affinity

There is a critical need for compounds that target cell surface integrin receptors for applications in cancer therapy and diagnosis. We used directed evolution to engineer the Ecballium elaterium trypsin inhibitor (EETI‐II), a knottin peptide from the squash family of protease inhibitors, as a new class of integrin‐binding agents. We generated yeast‐displayed libraries of EETI‐II by substituting its 6‐amino acid trypsin binding loop with 11‐amino acid loops containing the Arg‐Gly‐Asp integrin binding motif and randomized flanking residues. These libraries were screened in a high‐throughput manner by fluorescence‐activated cell sorting to identify mutants that bound to α_vβ₃ integrin. Select peptides were synthesized and were shown to compete for natural ligand binding to integrin receptors expressed on the surface of U87MG glioblastoma cells with half‐maximal inhibitory concentration values of 10–30 nM. Receptor specificity assays demonstrated that engineered knottin peptides bind to both α_vβ₃ and α_vβ₅ integrins with high affinity. Interestingly, we also discovered a peptide that binds with high affinity to α_vβ₃, α_vβ₅, and α₅β₁ integrins. This finding has important clinical implications because all three of these receptors can be coexpressed on tumors. In addition, we showed that engineered knottin peptides inhibit tumor cell adhesion to the extracellular matrix protein vitronectin, and in some cases fibronectin, depending on their integrin binding specificity. Collectively, these data validate EETI‐II as a scaffold for protein engineering, and highlight the development of unique integrin‐binding peptides with potential for translational applications in cancer. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

Contrasting solution conformations of peptides containing α,α-dialkylated residues with linear and cyclic side chains

The conformational properties of α,α-dialkylated amino acid residues possessing acyclic (diethylglycine, Deg: di-n-propylglycine, Dpg; di-n-butylglycine, Dbg) and cyclic (1-amino-cycloalkane-1-carboxylic acid, Ac_nc) side chains have been compared in solution. The five peptides studied by nmr and CD spectroscopy are Boc-Ala-Xxx-Ala-OMe, where Xxx = Deg(I). Dpg (II), Dbg (III), Ac₆c (IV), and Ac₇c (V). Delineation of solvent-shielded NH groups have been achieved by solvent and temperature dependence of NH chemical shifts in CDCl₃ and (CD₃)₂SO and by paramagnetic radical induced line broadening in pepiide III. In the Dxg peptides the order of solvent exposure of NH groups is Ala(1) > Ala(3) > Dxg(2), whereas in the Ac_nc peptides the order of solvent exposure of NH groups is Ala(1) > Ac_nc(2) > Ala(3). The nmr results suggest that Ac_nc peptides adopt folded β-turn conformations with Ala(1) and Ac_nc(2) occupying i + 1 and i + 2 positions. In contrast, the Dxg peptides favor extended C₅ conformations. The conformational differences in the two series are clearly borne out in CD studies. The solution conformations of peptides I-III are distinctly different from the β-turn structure observed in crystals. Low temperature nmr spectra recorded immediately after dissolution of crystals of peptide II provide evidence for a structural transition. Introduction of an additional hydrogen-bonding function in Boc-Ala-Dpg-Ala-NHMe (VI) results in a stabilization of a consecutive β-turn or incipient 3₁₀-helix in solution. © 1995 John Wiley & Sons, Inc.     

Vibrational analysis of peptides,polypeptides, and proteins. XVIII. Conformational sensitivity of the α-helix spectrum: αI- and αII-Poly(L-alanine)

The α_II-helix (? = ?70.47°, ψ = ?35.75°) is a structure having the same n and h as the (standard) α_I-helix (? = ?57.37°, ψ = ?47.49°). Its conformational angles are commonly found in proteins. Using an improved α-helix force field, we have compared the vibrational frequencies of these two structures. Despite the small conformational differences, there are significant predicted differences in frequencies, particularly in the amide A, amide I, and amide II bands, and in the conformation-sensitive region below 900 cm^?1. This analysis indicates that α_II-helices are likely to be present in bacteriorhodopsin [Krimm, S. & Dwivedi, A. M. (1982) Science 216 , 407–408].     

Flexibility of the pyranose ring in α- and β-D-glucoses

Conformational energies of α- and β-D -glucopyranoses were computed by varying all the ring bond angles and torsional angles using semiempirical potential functions. Solvent accessibility calculations were also performed to obtain a measure of solvent interaction. The results indicate that the ⁴C₁ (D ) chair is the most favored conformation, both by potential energy and solvent accessibility criteria. The ⁴C₁ (D ) chair conformation is also found to be somewhat flexible, being able to accommodate variations up to 10° in the ring torsional angles without appreciable change in energy. Observed solid-state conformations of these sugars and their derivatives lie in the minimum-energy region, suggesting that the substituents and crystal field forces play a minor role in influencing the pyranose ring conformation. Theory also predicts the variations in the ring torsional angles, i.e., CCCC < CCCO < CCOC, in agreement with the experimental results. The boat and twist-boat conformations are found to be at least 5 kcal mol^?1 higher in energy compared to the ⁴C₁ (D ) chair, suggesting that these forms are unlikely to be present in a polysaccharide chain. The ¹C₄ (D ) chair has energy intermediate between that of the ⁴C₁ (D ) chair and that of the twist-boat conformation. The calculated energy barrier between ⁴C₁ (D ) and ¹C₄ (D ) conformations is high—about 11 kcal mol^?1.     

Structural versatility of peptides from Cα, α-disubstituted glycines: Crystal-state conformational analysis of homopeptides from Cα-methyl,Cα-benzylglycine [(αMe)Phe]n

The molecular and crystal structures of one derivative and three homopeptides (from the di-to the tetrapeptide level) of the chiral, C^{α, α}-disubstituted glycine C^α-methyl, C^α-benzylglycine [(αMe)Phe], have been determined by x-ray diffraction. The derivative is mClAc-D -(αMe)Phe-OH, and the peptides are pBrBz-[D -(αMe)Phe]₂-NHMe, pBrBz-[D -(αMe)Phe]₃-OH hemihydrate, and pBrBz-[D -(αMe)Phe]₄-OtBu sesquihydrate. All (αMe)Phe residues prefer ?,ψ torsion angles in the helical region of the conformational map. The dipeptide methylamide and the tripeptide carboxylic acid adopt a β-turn conformation with a 1 ← 4 C?O…?H? N intramolecular H bond. The structure of the tripeptide carboxylic acid is further stabilized by a 1 ← 4 C?O…?H? O intramolecular H bond, forming an “oxy-analogue” of a β-turn. The tetrapeptide ester is folded in a regular (incipient) 3₁₀-helix. In general, the relationship between (αMe)Phe chirality and helix screw sense is opposite to that exhibited by protein amino acids. A comparison is made with the conclusions extracted from published work on homopeptides from other C^α-methylated α-amino acids. © 1993 John Wiley & Sons, Inc.     

Crystal structure of the bovine α-chymotrypsin:kunitz inhibitor complex. An example of multiple protein:protein recognition sites

The crystal structure of bovine α-chymotrypsin (α-CHT) in complex with the bovine basic pancreatic trypsin inhibitor (BPTI) has been solved and refined at 2.8 Å resolution (R-factor=0.18). The proteinase:inhibitor complex forms a compact dimer (two α-CHT and two BPTI molecules), which may be stabilized by surface-bound sulphate ions, in the crystalline state. Each BPTI molecule, at opposite ends, is contacting both proteinase molecules in the dimer, through the reactive site loop and through residues next to the inhibitor's C-terminal region. Specific recognition between α-CHT and BPTI occurs at the (re)active site interface according to structural rules inferred from the analysis of homologous serine proteinase:inhibitor complexes. Lys15, the P₁ residue of BPTI, however, does not occupy the α-CHT S₁ specificity pocket, being hydrogen bonded to backbone atoms of the enzyme surface residues Gly216 and Ser217. © 1997 John Wiley & Sons, Ltd.     

Design and characterization of a model αβ peptide

CD and nmr spectroscopy were used to compare the conformational properties of two related peptides. One of the peptides, Model AB, was designed to adopt a helix-turn-extended strand (αβ) tertiary structure in water that might be stabilized by hydrophobic interactions between two leucine residues in the amino-terminal segment and two methionine residues in the carboxyl terminal segment. The other peptide, AB Helix, has the same amino acid sequence as Model AB except that it lacks the-Pro-Met-Thr-Met-Thr-Gly segment at the carboxyl-terminus. Although the carboxyl-terminal segment of Model AB was found to be unstructured, its presence increases the number of residues in a helical conformation, shifts the pKas of three ionizable side chains by 1 pH unit or more compared to an unstructured peptide, stabilizes the peptide as a monomer in high concentrations of ammonium sulfate, increases the conformational stability of residues at the terminal ends of the helix, and results in many slowly exchanging amide protons throughout the entire backbone of the peptide. These results suggest that interactions between adjacent segments in a small peptide can have significant structure organizing effects. Similar kinds of interactions may be important in determining the structure of early intermediates in protein folding and may be useful in the de novo design of independently folding peptides. © 1995 John Wiley & Sons, Inc.     

Structures of peptides from α-amino acids methylated at the α-carbon,

The structural preferences of peptides (and depsipeptides) from the achiral MeAib and Hib residues, and the chiral Iva, (αMe) Val, (αMe) Leu, and (αMe) Phe residues, as determined by conformational energy computations, x-ray diffraction analyses, and ¹H-nmr and spectroscopic studies, are reviewed and compared with literature data on Aib-containing peptides. The results obtained indicate that helical structures are preferentially adopted by peptides rich in these α-amino acids methylated at the α-carbon. Intriguing experimental findings on the impact of the chirality of Iva, (αMe) Val, and (αMe) Phe residues on helix screw sense are illustrated. © 1993 John Wiley & Sons, Inc.     

Kinetics of coil to α-helix to β-structure transitions of poly(L-ornithine) in low concentrations of sodium dodecyl sulfate

Conformational changes of poly(L-ornithine) [(Orn)_n] were studied in a sodium dodecyl sulfate (NaDodSO₄) solution by CD. (Orn)_n adopted an unstable and a stable helical structure below and above the NaDodSO₄ concentration range where β-structure was favored, respectively. CD stopped-flow was used to monitor the transitions from coil to the unstable helix, from the helix to β-structure, and from coil to β-structure. Only the rate of the helix to β-structure transition was accelerated by an increase in NaDodSO₄ concentration, whereas the rates of the others were independent of NaDodSO₄ concentration. The fractions of coil, α-helix, and β-structure in each conformation of (Orn)_n caused by NaDodSO₄ were computed by simulating a mixed spectrum of typical CD spectra for these structures to the experimentally obtained spectrum. The contents of the unstable and stable helical structures were less than 50 and 73%, respectively.