Right-handed Screw Sense Research Articles

Reaction, Recognition, Relay: Anhydride Hydrolysis Reported by Conformationally Responsive Fluorinated Foldamers in Micelles.

Natural membrane receptors are proteins that can report on changes in the concentration of external chemical messengers. Messenger binding to a receptor produces conformational changes that are relayed through the membrane into the cell; this information allows cells to adapt to changes in their environment. Artificial membrane receptors (R)-1 and (S)-1 are helical α-aminoisobutyric acid (Aib) foldamers that replicate key parts of this information relay. Solution-phase 19F NMR spectroscopy of zinc(II)-capped receptor 1, either in organic solvent or in membrane-mimetic micelles, showed messenger binding produced an enrichment of either left- or right-handed screw-sense; the chirality of the bound messenger was relayed to the other receptor terminus. Furthermore, in situ production of a chemical messenger in the external aqueous environment could be detected in real-time by a racemic mixture of receptor 1 in micelles. The hydrolysis of insoluble anhydrides produced carboxylate in the aqueous phase, which bound to the receptors and gave a distinct 19F NMR output from inside the hydrophobic region of the micelles.

Cα-Methyl-l-valine: A Preferential Choice over α-Aminoisobutyric Acid for Designing Right-Handed α-Helical Scaffolds.

In synthetic peptides containing Gly and coded α-amino acids, one of the most common practices to enhance their helical extent is to incorporate a large number of l-Ala residues along with noncoded, strongly foldameric α-aminoisobutyric acid (Aib) units. Earlier studies have established that Aib-based peptides, with propensity for both the 310- and α-helices, have a tendency to form ordered three-dimensional structure that is much stronger than that exhibited by their l-Ala rich counterparts. However, the achiral nature of Aib induces an inherent, equal preference for the right- and left-handed helical conformations as found in Aib homopeptide stretches. This property poses challenges in the analysis of a model peptide helical conformation based on chirospectroscopic techniques like electronic circular dichroism (ECD), a very important tool for assigning secondary structures. To overcome such ambiguity, we have synthesized and investigated a thermally stable 14-mer peptide in which each of the Aib residues of our previously designed and reported analogue ABGY (where B stands for Aib) is replaced by Cα-methyl-l-valine (L-AMV). Analysis of the results described here from complementary ECD and 1H nuclear magnetic resonance spectroscopic techniques in a variety of environments firmly establishes that the L-AMV-containing peptide exhibits a significantly stronger preference compared to that of its Aib parent in terms of conferring α-helical character. Furthermore, being a chiral α-amino acid, L-AMV shows an intrinsic, extremely strong bias for a quite specific (right-handed) screw sense. These findings emphasize the relevance of L-AMV as a more appropriate unit for the design of right-handed α-helical peptide models that may be utilized as conformationally constrained scaffolds.

Ambidextrous α,γ-Hybrid Peptide Foldamers.

Molecular chirality is ubiquitous in nature. The natural biopolymers, proteins and DNA, preferred a right-handed helical bias due to the inherent stereochemistry of the monomer building blocks. Here, we are reporting a rare co-existence of left- and right-handed helical conformations and helix-terminating property at the C-terminus within a single molecule of α,γ-hybrid peptide foldamers composed of achiral Aib (α-aminoisobutyric acid) and 3,3-dimethyl-substituted γ-amino acid (Adb; 4-amino-3,3-dimethylbutanoic acid). At the molecular level, the left- and right-handed helical screw sense of α,γ-hybrid peptides are representing a macroscopic tendril perversion. The pronounced helix-terminating behaviour of C-terminal Adb residues was further explored to design helix-Schellman loop mimetics and to study their conformations in solution and single crystals. The stereochemical constraints of dialkyl substitutions on γ-amino acids showed a marked impact on the folding behaviour of α,γ-hybrid peptides.

Engineering the Structure of an N-Terminal β-Turn To Maximize Screw-Sense Preference in Achiral Helical Peptide Chains

Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 310 helical conformations in which enantiomeric left- and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a right-handed screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.

Optically Active Organotin Compounds Derived from β-Pinene. The Quest for Chiral Polystannanes

series of enantiomerically pure bis(myrtanyl)tin compounds, cis-Myr2SnX2 (1, X = Ph; 3, X = Cl; 5, X = H) and trans-Myr2SnX2 (2, X = Ph; 4, X = Cl; 6, X = H) were prepared starting from (–)-1S-β-pinene and characterized by multinuclear NMR spectroscopy and in case of 3 and 4 also by X-ray crystallography. The reduction of 3 and 4 with Mg selectively produced pentastannane rings, cyclo-(cis-Myr2Sn)5 (7) and cyclo-(trans-Myr2Sn)5 (8), while the dehydropolymerization of 5 and 6 produced a mixture of polystannanes, poly(cis-Myr2Sn)n (9) or poly(trans-Myr2Sn)n (10), and oligomers that could not be separated. The pentastannane rings gave rise to UV absorptions at λmax 219 and 217 nm, which were assigned to σ → σ* transitions of the Sn−Sn bonds. Due to the increased σ-electron delocalization, the polystannanes 9 and 10 show red-shifted UV absorptions at λmax 416 and 417 nm. The CD spectra of the polystannanes 9 and 10 reveal a positive cotton effect at λmax 422 and 425 nm, consistent with the idea that the chiral information is transferred from the UV-inactive myrtanyl groups to the polymer backbone, which most likely adopts a helical conformation with the right-handed screw sense being in excess.

Chiral interaction in Gly‐capped N‐terminal motif of 310‐helix and domino‐type induction in helix sense

Chiral interaction of helical peptide with chiral molecule, and concomitant induction in its helix sense have been demonstrated in optically inactive nonapeptide (1) possessing Gly at its N-terminus: H-Gly-(Delta(Z)Phe-Aib)(4)-OCH(3) (1: Delta(Z)Phe = Z-dehydrophenylalanine; Aib = alpha-aminoisobutyric acid). Spectroscopic measurements [mainly nuclear magnetic resonance (NMR) and circular diochroism (CD)] as well as theoretical simulation have been carried out for that purpose. Peptide 1 in the 3(10)-helix tends to adopt preferentially a right-handed screw sense by chiral Boc-L-amino acid (Boc: t-butoxycarbonyl). Induction in the helix sense through the noncovalent chiral domino effect should be derived primarily from the complex supported by the three-point coordination on the N-terminal sequence. Thus the 3(10)-helical terminus consisting of only alpha-amino acid residues enables chiral recognition of the Boc-amino acid molecule, leading to modulation of the original chain asymmetry. Dynamics in the helix-sense induction also have been discussed on the basis of a low-temperature NMR study. Furthermore, the inversion of induced helix sense has been achieved through solvent effects.

Examination of structural characteristics of the potent oxytocin antagonists [dPen1,Pen6]-OT and [dPen1,Pen6, 5-tBuPro7]-OT by NMR, raman, CD spectroscopy and molecular modeling

The synthesis and biological evaluation of penicillamine(6)-5-tert-butylproline(7)-oxytocin analogs and comparison with their proline(7)-oxytocin counterparts has led to the discovery of two potent oxytocin (OT) antagonists: [dPen(1),Pen(6)]-oxytocin (1, pA(2) = 8.22, EC(50) = 6.0 nM) and [dPen(1),Pen(6),5-tBuPro(7)]-oxytocin (2, pA(2) = 8.19, EC(50) = 6.5 nM). In an attempt to understand the conformational requirements for their biological activity, spectroscopic analyses of 1 and 2 were performed using (1)H NMR, laser Raman and CD techniques. In H(2)O, oxytocin analogs 1 and 2 exhibited cis-isomer populations of 7% and 35%, respectively. Measurement of the amide proton temperature coefficients revealed solvent shielded hydrogens for Gln(4) and Pen(6) in the major trans-conformer of 1 as well as for Gln(4) in the minor cis-conformer of 2. Few long-distance NOEs were observed, suggesting conformational averaging for analogs 1 and 2 in water; moreover, a lower barrier (16.6 +/- 0.2 kcal/mol) for isomerization of the amide N-terminal to 5-tBuPro(7) relative to OT was calculated from measuring the coalescence temperature of the Gly(9) backbone NH signals in the NMR spectra of 2. Observed bands in the Raman spectra of 1 and 2 correspond to C(beta)-S-S-C(beta) dihedral angles of +110-115 degrees and +/-90 degrees , respectively. In water, acetonitrile and methanol, the CD spectra for 1 exhibited a positive maximum around 236-239 nm; in trifluoroethanol, the spectra shifted and a negative maximum was observed at 240 nm. The CD spectra of 2 were unaffected by solvent changes and exhibited a negative maximum at 236-239 nm. The CD and Raman data both suggested that a conformation having a right-handed screw sense about the disulfide and a chi(CS-SC) dihedral angle value close to 115 degrees was favored for analog 1 in water, methanol and acetonitrile, but not trifluoroethanol, where a +/-90 degrees angle was favored. Analog 2 was more resilient to conformational change about the disulfide, and adopted a preferred disulfide geometry corresponding to a +/-90 degrees chi(CS-SC) dihedral angle. Monte Carlo conformational analysis of analogs 1 and 2 using distance restraints derived from NMR spectroscopy revealed two prominent conformational minima for analog 1 with disulfide geometries around +114 degrees and +116 degrees . Similar analysis of analog 2 revealed one conformational minimum with a disulfide geometry around +104 degrees . In sum, the conformation about the disulfide in [dPen(1),Pen(6)]-OT (1) was shown to be contingent on environment and in TFE, adopted a geometry similar to that of [dPen(1),Pen(6),5-tBuPro(7)]-OT (2) which appeared to be stabilized by hydrophobic interactions between the 5-tBuPro(7) (5R)-tert-butyl group, the Leu(8) isopropyl sidechain and the Pen(6)beta-methyl substituents. In light of the conformational rigidity of 2 about the disulfide bond, and the similar geometry adopted by 1 in TFE, a S-S dihedral angle close to +110 degrees may be a prerequisite for their binding at the receptor.

Noncovalent chiral domino effect on one-handed helix of nonapeptide containing a midpoint L-residue.

We here clarify whether noncovalent chiral domino effect characterized by the terminal interaction of a helical peptide with a chiral small molecule can alter the helical stability of N-deprotected peptides containing an L-residue covalently incorporated into the inner position. Two nonapeptides consisting of the midpoint L-leucine (1) or L-phenylalanine (2) and the achiral helix-forming residues were employed. NMR and IR spectroscopy and energy calculation indicated that both peptides adopt a 3(10)-helical conformation in chloroform. They strongly preferred a right-handed screw sense because of the presence of the midpoint L-residue. These original right-handed screw senses were retained on addition of chiral Boc-amino acid, but their helical stabilities clearly depended on its added chirality. Here, Boc-L-amino acid stabilizes the original right-handed helix, whereas the corresponding Boc-D-amino acid tends to less stabilize or destabilize it. This tendency was not observed for the corresponding N-Boc-protected peptides 1 and 2, strongly suggesting that the N-terminal amino group is required for controlling the stabilization of the original right-handed helix. Therefore, noncovalent chiral domino effect in peptides 1 and 2 can contribute even to the helical stability of a chiral peptide prevailing one-handed helix strongly through the midpoint L-residue. In addition, the N-terminal moiety of a 3(10)-helical peptide was found to generate chiral discrimination in complexation process with racemic additives.

Noncovalent domino effect on helical screw sense of chiral peptides possessing C-terminal chiral residue.

Recently, a novel chiral intermolecular interaction was found in an N-deprotected achiral nonapeptide that undergoes the predominance of one-handed screw sense through the addition of chiral small carboxylic acid (Inai, Y.; Tagawa, K.; Takasu, A.; Hirabayashi, T.; Oshikawa, T.; Yamashita, M. J. Am. Chem. Soc. 2000, 122, 11731). We here clarify to what extent such noncovalent chiral domino effect affects the helical screw sense of an N-deprotected chiral peptide. Two chiral peptides consisting of C-terminal L-Leu (1) or L-Leu(2) (2) and the preceding achiral helical octapeptide segment were employed. NMR and IR spectroscopy, and energy calculation indicated that both peptides adopt a helical conformation in chloroform. Peptide 1 showed a small excess of a left-handed screw sense for the achiral helical octapeptide, but peptide 2 strongly preferred a right-handed screw sense. The addition of chiral Boc amino acid to a chloroform solution of peptide 1, depending on its chirality, underwent a unique helix-to-helix transition or led to remarkable stabilization of the original left-handed screw sense. Peptide 2 retained the original right-handed screw sense on addition of chiral Boc-amino acid, but its helical stability changed to some extent depending on its added chirality. Therefore, the importance of noncovalent domino effect for controlling the helical screw sense or helical stability of a chiral peptide has been demonstrated here for the first time. In addition, we here have presented a unique system that both N-terminal noncovalent and C-terminal covalent domino effects operate simultaneously on the helical screw sense of a single achiral segment and have compared both powers for inducing the screw sense bias.

Screw sense preference of non-polarL-amino acid residues second from the N-terminal position

To understand the positional effects of a single chiral residue on the helical screw sense of an achiral segment, we adopted five kinds of peptides Boc-Aib-X*-(Aib-ΔZPhe)2-Aib-OMe (Boc, t-butoxycarbonyl; Aib, α-aminoisobutyric acid; ΔZPhe, (Z)-dehydrophenylalanine; OMe, methoxy), wherein the X* residue is an L-residue of leucine (Leu), alanine (Ala), valine (Val), phenylalanine (Phe), or 1-naphthylalanine (Nap). Here the segment -(Aib-ΔZPhe)2-Aib-OMe was employed as an achiral backbone for generating two “enantiomeric” (left-handed/right-handed) helices. All of the peptides are folded into a 310-type helical conformation in chloroform, as evidenced by FT-IR and 1H NMR techniques. A CD analysis of these peptides indicates that they adopt both left-handed and right-handed helices, and that the prevailing screw sense as well as the screw sense bias depend on the type of solvent. Thus, the L-residue located at the position second from the N-terminus plays a unique role for energetically permitting both helices. These peptides also undergo a solvent-induced interconversion between both helices. The rank order of the penultimate L-residues for inducing a right-handed screw sense is Val > Leu ∼ Ala > Phe > Nap, of which the reverse order represents the tendency to promote a left-handed screw sense. The prevailing screw sense induced by the penultimate L-residue is also discussed on the basis of conformational energy calculations. In conclusion, we here have been able to express experimentally a unique screw sense preference of these non-polar L-amino acids.

Solvent Dependence on the Preference of Helical Screw Sense: Effect of l-Leu Residue Second from N-Terminal on Screw Sense in Achiral Peptide

To clarify which helical screw sense is preferred when one l-residue is introduced into the second position from N-terminal of an achiral helical segment, we prepared Boc-Aib-l-Leu-(Aib-ΔZPhe)2-Aib-OMe (1: Boc = t-butoxycarbonyl; Aib = α-aminoisobutyric acid; ΔZPhe = Z-dehydrophenylalanine; OMe = methoxy). Here the segment -(Aib-ΔZPhe)2-Aib-OMe was used as an achiral backbone composed of two “enantiomeric” (left-/right-handed) helices. Peptide 1 was found to form a 310-type helical conformation in chloroform, from FT IR (the position of amide I band) and 1H NMR (difference nuclear Overhauser effect and solvent accessibility of NH resonances) measurements. Interestingly, CD patterns of peptide 1 changed with types of solvents: i.e., exciton couplets around 280 nm with a negative peak at longer wavelengths in chloroform and with a positive peak at longer wavelengths in methanol or in tetrahydrofuran. Consequently, the helical segment prefers a right-handed screw sense in chloroform and a left-handed one i...

Terminal effect of chiral residue on helical screw sense in achiral peptides

To understand the terminal effect of chiral residue for determining a helical screw sense, we adopted five kinds of peptides I–V containing N- and/or C-terminal chiral Leu residue(s): Boc–L-Leu–(Aib–ΔPhe)2–Aib–OMe (I), Boc–(Aib–ΔPhe)2–L-Leu–OMe (II), Boc–L-Leu–(Aib–ΔPhe)2–L-Leu–OMe (III), Boc–D-Leu–(Aib–ΔPhe)2–L-Leu–OMe (IV), and Boc–D-Leu–(Aib–ΔPhe)2–Aib–OMe (V). The segment –(Aib–ΔPhe)2– was used for a backbone composed of two “enantiomeric” (left-/right-handed) helices. Actually, this could be confirmed by 1H-nmr [nuclear Overhauser effect (NOE) and solvent accessibility of NH resonances] and CD spectroscopy on Boc–(Aib–ΔPhe)2–Aib–OMe, which took a left-/right-handed 310-helix. Peptides I–V were also found to take 310-type helical conformations in CDCl3, from difference NOE measurement and solvent accessibility of NH resonances. Chloroform, acetonitrile, methanol, and tetrahydrofuran were used for CD measurement. The CD spectra of peptides I–III in all solvents showed marked exciton couplets with a positive peak at longer wavelengths, indicating that their main chains prefer a left-handed screw sense over a right-handed one. Peptide V in all solvents showed exciton couplets with a negative peak at longer wavelengths, indicating it prefers a right-handed screw sense. Peptide IV in chloroform showed a nonsplit type CD pattern having only a small negative signal around 280 nm, meaning that left- and right-handed helices should exist with almost the same content. In the other solvents, peptide IV showed exciton couplets with a negative peak at longer wavelengths, corresponding to a right-handed screw sense. From conformational energy calculation and the above 1H-nmr studies, an N- or C-terminal L-Leu residue in the lowest energy left-handed 310-helical conformation was found to take an irregular conformation that deviates from a left-handed helix. The positional effect of the L-residue on helical screw sense was discussed based on CD data of peptides I–V and of Boc–(L-Leu–ΔPhe)n–L-Leu–OMe (n = 2 and 3). © 1999 John Wiley & Sons, Inc. Biopoly 49: 551–564, 1999

Ambidextrous molecules: Cylindrical peptide structures formed by fusing left- and right-handed helices

The handedness or chirality of molecules, organisms, and elementary particles has been widely appreciated, vindicating Pasteur’s perceptive generalization, Luni-vers est dissymktrique. Ambidexterity is rare not only in biological organisms but also in molecules. One of the most striking chiral features in biopolymers is the twist or handedness of the helices that are frequently formed. Cylindrical helical structures formed by polypeptide chains are an important constituent of peptide and protein structure, The most widespread helical structures are the alpha-helix and 310-helix, both of which have a right-handed screw sense in proteins, determined by the L configuration of the component amino acids. Peptide sequences with alternating L and D residues occur in the membrane channel-forming I 5-residue peptide gramicidin A, resulting in a large diameter cylindrical structure formed by wrapping beta strands about the helix axis.’ Alternating L,D sequences in cyclic peptides have yielded novel tubular stack. Helical polymers with alternating left- and right-handed blocks have been studies in polyisocyanates, providing new insights into the effect of chiral biases on polymer properties. In order to develop novel synthetic structures using chiral blocks, we have investigated peptides with strong helix-forming tendencies generated so as to fuse left- and right-handed cylindrical screws in the same molecule. We describe below the structural characterization of a 14-residue hydrophobic peptide containing two heptapeptide blocks of opposite chirality.

The crystal state conformation of Aib-rich segments of peptaibol antibiotics.

Ac-(Aib-Ala)3-OH (a protected segment of the peptaibols gliodeliquescin and paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of [Leu]7-gliodeliquescin), Z-Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsin, and hypelcin), and Ac-Aib-Pro-(Aib-Ala)2-OMe and Z-Aib-Pro-(Aib-Ala)2-OMe, which represent differently N(alpha)-protected 1-6 segments of alamethicin and hypelcin, have been synthesized by solution methods. The crystal-state conformations of these five Aib-containing peptides have been determined by X-ray diffraction analysis. We have confirmed that the 3(10)-helical structure is preferentially adopted by Aib-rich short peptides. An experimentally unambiguous proof for the 3(10)-->alpha-helix conversion has been provided by the two differently N-blocked -Aib-Pro-(Aib-Ala)2-OMe hexapeptides. The beta-bend ribbon conformation, commonly observed in the (Aib-Pro)n sequential oligopeptides, is not found in the -Aib-Pro-Aib-Ala-Aib-Ala-sequence. As expected on the basis of the L-configuration of the C(alpha)-monoalkylated residues, a right-handed helix screw sense was found in all peptides investigated.

Acetyl-ΔPhe-L-Ala-ΔPhe-D-Ala Methyl Ester

The peptide chain of acetylphenylalanine-L-alanine-phenylalanine-D-alanine methyl ester, C 27 H 30 N 4 O 6 , adopts a 3 10 -helical conformation having right-handed screw sense. The 3 10 -helix is stabilized by intramolecular hydrogen bonds, between CO of the acetyl group and NH of ΔPhe 3 , and between CO of ΔPhe 1 and NH of D-Ala 4 . The hydrogen bonds form two consecutive ten-membered rings whose (φ, ψ) torsion angles are quite close to the standard values for type-III β-turns. In the crystal, the molecules are linked head-to-tail by intermolecular hydrogen bonds to form continuous helical columns. These are aligned along axes parallel to the c axis, with neighbouring columns running in opposite directions. There are no lateral hydrogen bonds between helical columns, but only hydrophobic interactions provided by the interdigitation of apolar side chains of the dehydro-phenylalanine residues, as well as of the C-terminal methyl ester groups.

Chiroptical Absorption and Luminescence Spectra of a Dissymmetric Osmium(II)−Polypyridyl Complex Containing an Optically Active Bis(bipyridine)-Type Ligand of Well-Defined Structural Chirality

Chiroptical absorption and luminescence spectra are reported for a novel Os(II)−polypyridyl complex in which Os(II) is coordinated to one achiral bidentate ligand and a chiral quadridentate ligand. The achiral ligand is 4,4‘-dimethyl-2,2‘-bipyridine (DMbpy), and the chiral ligand is a bisbipyridine-type molecule formed by linking two optically active (−)-[4,5]-pineno-2,2‘-bipyridine molecules together via a (CH2)6 chain bridge. This chiral ligand is one of a family of ligands often referred to as chiragens, and here it is denoted by CG[6], where [6] identifies the number of carbon atoms in the chain bridge. The coordination core of the complex has a three-bladed propeller-like structure formed by three Os(II)−bipyridyl chelate rings. This tris(bipyridyl)Os(II) core structure has approximate trigonal-dihedral (D3) symmetry, and the propeller-like assembly of its three chelate rings has a right-handed screw sense (or helicity). The overall complex, denoted by Δ-[Os(CG[6])(DMbpy)]2+, has C2 point-group symme...

Solution structure of peptides containing two dehydro‐phenylalanine residues: A CD investigation

The peptides Ac-delta Phe-Ala-delta Phe-NH-Me (1), Ac-delta Phe-Val-delta Phe-NH-Me (2), Ac-delta Phe-Gly-delta Phe-Ala-OMe (3), and Boc-Ala-delta Phe-Gly-delta Phe-Ala-OMe (4), containing two dehydro-phenylalanine (delta Phe) residues, were synthesized and the solution structure investigated in various solvents. The nmr and CD measurements indicate that all the dehydropeptides examined adopt 3(10)-helical conformations in solution. The tripeptides 1 and 2 exhibited an intense negative CD exciton couplet, which was assigned to the right-handed screw sense, while the tetrapeptide 3 displayed a CD couplet having opposite sign, which was assigned to the left-handed helical sense. In the pentapeptide 4 the sense of the helix was found to vary with solvent and temperature, as demonstrated by the sign reversal of the CD spectrum. The right-handed sense dominates in hexafluoro-2-propanol, whereas a left-handed helix prevails in chloroform, acetonitrile and methanol. A crucial role for this behavior is likely to be played by the two alanine residues positioned respectively at the head and tail of the sequence, which favor conformations having opposite screw senses.

Critical Main-Chain Length for Conformational Conversion From 310-Helix to α-Helix in Polypeptides

To assess the minimal peptide length required for the stabilization of the alpha-helix relative to the 3(10)-helix in Aib-rich peptides, we have solved the X-ray diffraction structures of the terminally blocked sequential hexa- and octapeptides with the general formula-(Aib-L-Ala)n-(n = 3 and 4, respectively). The hexapeptide molecules are completely 3(10)-helical with four 1----4 intramolecular N-H . . . O = C H-bonds. On the other hand, the octapeptide molecules are essentially alpha-helical with four 1----5 H-bonds; however, the helix is elongated at the N-terminus, with two 1----4 H-bonds, giving these molecules a mixed alpha/3(10)-helical character. In both compounds the right-handed screw sense of the helix is dictated by the presence of the Ala residues of L-configuration. This study represents the first experimental proof for a 3(10)----alpha-helix conversion in the crystal state induced by peptide backbone lengthening only.

Screw sense differentiating polymerization of achiral isocyanides

Polymerization of achiral isocyanides p-XC6H4NC (X = MeO, Me, H, Cl)by nickel(II) chloride in the presence of (S)-2-isocyanoisovaleric acid methyl or t-butyl ester gives rise to optically active polymers [p-XC6H4NC]n with an excess of right-handed screw sense.

Alpha-Helices and a new polypeptide fold in poly-beta-benzyl-L-aspartate.

IN Moffitt's expression for the variation of the optical rotation of an L-polypeptide in the α-helical form with wave-length1,2, the constant b 0 has been found to have values between − 400 and − 700 deg. cm.2/decimole; the negative value is certainly associated with a right-handed screw sense in poly-L-alanine3. Recently, values up to 631° have been reported for poly-β-benzyl-L-aspartate ([CO.NH.CHCH2CO.OCH2C6H5]n) in chloroform solution by Blout and Karlson4. This positive value of b 0 may indicate either the ‘structural’ anomaly of a left-handed screw sense, or alternatively an ‘optical’ anomaly due to interaction between peptide and side-chain chromophores or consequent upon some minor structural peculiarity. We have confirmed the anomalous result and have examined the polymer by a variety of techniques.