Hybrid peptide hairpins containing alpha- and omega-amino acids: Conformational analysis of decapeptides with unsubstituted beta-, gamma-, and delta-residues at positions 3 and 8

The effects of inserting unsubstituted omega-amino acids into the strand segments of model beta-hairpin peptides was investigated by using four synthetic decapeptides, Boc-Lcu-Val-Xxx-Val-D-Pro-Gly-Leu-Xxx-Val-Val- OMe: pepticle 1 (Xxx=Gly), pepticle 2 (Xxx=beta Gly=beta hGly=homoglycine, beta-glycine), pepticle 3 (Xxx=gamma Abu=gamma-aminobutyric acid), pepticle 4 (Xxx= delta Ava=delta-aminovaleric acid). H-1 NMR studies (500 MHz, methanol) reveal several critical cross-strand NOEs, providing evidence for P-hairpin conformations in peptides 2-4. In peptide 3, the NMR results support the formation of the nucleating turn, however, evidence for cross-strand registry is not detected. Single-crystal X-ray diffraction studies of peptide 3 reveal a beta-hairpin conformation for both molecules in the crystallographic asymmetric unit, stabilized by four cross-strand hydrogen bonds, with the gamma Abu residues accommodated within the strands. The D-Pro-Gly segment in both molecules (A,B) adopts a type II' beta-turn conformation. The circular dichroism spectrum for peptide 3 is characterized by a negative CD band at 229 rim, whereas for peptides 2 and 4, the negative band is centered at 225 nm, suggesting a correlation between the orientation of the amide units in the strand segments and the observed CD pattern.

N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yI)colcemid, a probe for different classes of colchincine-binding site on tubulin

The nature of binding of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-colcemid (NBD-colcemid), an environment-sensitive fluorescent analogue of colchicine, to tubulin was tested. This article reports the first fluorometric study where two types of binding site of colchincine analogue on tubulin were detected. Binding of NBD-colcemid to one of these sites equilibrates slsowly. NBD-colcemid competes with colchicine for this site. Binding of NBD-colcemid to this site also causes inhibition of tubulin self-assembly. In contrast, NBD-colcemid binding to the other site is characterised by rapid equilibration and lack of competition with colchicine. Nevertheless, binding to this site is highly specific for the cholchicine nucleus, as alkyl-NBD analogues have no significant binding activity. Fast-reaction-kinetic studies gave 1.76 × 105 M–1 s–1 for the association and 0.79 s–1 for the dissociation rate constants for the binding of NBD-colcemid to the fast site of tubulin. The association rate constants for the two phases of the slow site are 0.016 × 10–4 M–1 s–1 and 3.5 × 10–4 M–1 respectively. These two sites may be related to the two sites of colchicine reported earlier, with binding characteristics altered by the increased hydrophobic nature of NBD-colcemid.

Transformation reactions of α-pinene—I : Reactions of ethyl (−)-2,2-dimethyl-3-ketocyclobutyl acetate

Some transformation reactions of α-pinene to give 4- and 3-membered ring compounds, not hitherto obtained from this source, are described. The study furnished a convenient method of preparation of the optically active cyclobutanone IVa, the title compound which served as the key substrate for all the transformations reported.

Studies in oxasteroids—I : Synthesis of 3-cyano-3-methyl-7-methoxychroman-4-one and the structure of an “abnormal” product

A synthesis of 3-cyano-3-methyl-7-methoxychroman-4-one is reported. The structure of an “abnormal” product obtained during isomerization (III) with potassium t-butoxide in t-butanol, followed by alkylation with methyl iodide has been proved to be 3-t-butoxy-2-cyano- 2-mehthyl-2′,4′-dimethoxypropiophenone (IVa).

Studies in sesquiterpenes—XXVI : Synthesis of 2,2,6-trimethyl-3-oxo-1-carbomethoxybicyclo[0,3,3]octane, a degradation product of patchouli alcohol

The synthesis of the title compound is described and results of some experiments on the degradation of patchouli alcohol are reported.

Addition of hydrogen cyanide to 9-methyl- Δ4-octalone-3 and 9β-methyl-8β-hydroxy- Δ4-octalone-3

Addition of hydrogen cyanide to 9-methyl-Δ4-octalone-3 (IIb), as a model, yielded both cis- and trans-ketonitriles the configurations of which are assigned on the basis of IR spectra of the hydrolysed products. Similar addition of hydrogen cyanide to 9β-methyl-8β-hydroxy-Δ4-octalone-3 (IIc) gave the corresponding cis- and trans-hydroxy-keto-nitriles, configurations of which were proved by their conversion into cis- and trans-keto-nitriles obtained in the model study. In contrast to the model experiment where the trans-product predominated, the cis-isomer was the major product of addition to IIc.

A designed (3-hairpin peptide in crystals

Beta-hairpin structures have been crystallographically characterized only in very short acyclic peptides, in contrast to helices. The structure of the designed beta-hairpin, t-butoxycarbonyl-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe in crystals is described. The two independent molecules of the octapeptide fold into almost ideal beta-hairpin conformations with the central D-Pro-Gly segment adopting a Type II' beta-turn conformation. The definitive characterization of a beta-hairpin has implications for de novo peptide and protein design, particularly for the development of three- and four-stranded beta-sheets.

The specificity of the colour reaction between ammonia and 3-phenyl-2-thiohydantoin

The colour reaction between 3-phenyl-2-thiohydantoin and ammonia is studied quantitatively. Determinations of 0.1–0.6 μmoles of 3-phenyl-2-thiohydantoin are possible with a precision close to 2%. In analyses of amino acid mixtures for glycine after conversion to 3-phenyl-2-thiohydantoin, only derivatives of serine and threonine interfere to a slight extent. The specificity of the primary colour reaction with ammonia, and the structural requirements for it are discussed; a structure for the pigment species is proposed.

Carotenoids In 3 Stages Of Ripening Of Mango

The distribution of carotenoids, both qualitative and quantitative, during 3 stages of ripening of mango has been studied using chromatographic, spectroscopic and chemical methods. There was an increase in content as well as in number of carotenoids during ripening. The present study showed there were 15, 14 and 17 different carotenoids in the unripe, partially ripe and fully ripe mangoes, respectively. Even though phytofluene (39.26%) was the major carotenoid in the partially ripe mango, β-carotene constituted the major carotenoid in the unripe (37.47%) and fully ripe mango (50.64%). cis-β-Carotene was present only in the fully ripe mango. Only the unripe mango contained ζ-carotene, whereas γ-carotene was present in all the 3 stages of ripening. The major xanthophyll present in the unripe mango was mutatoxanthin (9.44%), whereas auroxanthin constituted the major hydroxylated carotenoid of the partially ripe (5.07%) and fully ripe (10.40%) mangoes. The percent of cryptoxanthin dropped to lower levels during ripening. As ripening proceeded, lutein completely is appeared. There were significant quantities of eaxanthin in the partially ripe and fully ripe mango. Epoxy carotenoids such as 5,6-monoepoxy-β-carotene, mutatochrome, cis-violaxanthin, luteoxanthin, mutatoxanthin and auroxanthin were observed in all 3 stages of ripening.

On the conformations of isomeric trimethyl -methylcyclohexane-1,2,3-tricarboxylates

A study has been made of the stereochemistry of three of the four possible configurational isomers of trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate. Two of the isomers undergo highly stereoselective methylation at the 3-position; the third cannot be methylated under similar conditions. Conformations have been suggested for these three isomers on the basis of n.m.r. results. It is thought that axial ester groups at the 1-position in the first two solvate the axial protons at the 3-position and facilitate their removal by trityl anion, while in the third, which has an axial methyl at the 1-position, the effect is not possible and the anion is not formed. The role of A(1.3) strain in causing the high stereoselectivity and position-specificity in the two cases where alkylation does take place and the reasons for slow inversion at the anion centre at position 3 in one of them are discussed.