Synthesis,conformation, and membrane modifying properties of the trikoningin KB lipopeptaibols: Effect of hydrophobicity and chirality in position 1

Summary We synthesized by solution-phase methods the naturally occurring, 10-amino acid residue lipopeptaibol antibiotics trikoningins KBI and KBII, and the [l-Iva¹] KB analogue, in which the amino acid in position 1 is different, with the aim at investigating the effect of hydrophobicity and chirality in that position. A solution conformational analysis, using FT-IR absorption and CD techniques, indicated that all of the three decapeptides are predominantly helical in a membrane-mimetic environment. Permeability measurements showed an increase of the activity from the [Aib¹] peptide to the more hydrophobic [Iva¹] peptides. Conversely, the effect of a change in chirality, obtained by replacingd-Iva¹ withl-Iva, turned out to be of minor significance.     

Gamma Interferon Is a Major Suppressive Factor Produced by Activated Human Peripheral Blood Lymphocytes That Is Able To Inhibit Foamy Virus-Induced Cytopathic Effects

The activation of human peripheral blood lymphocytes by mitogens or by triggering the T-cell receptor with anti-CD3 antibodies leads to the production of a potent soluble inhibitory activity against foamy virus-induced cytopathic effects in vitro. The inhibitory activity acts in a species-specific manner. As a consequence, the isolation of foamy viruses from blood lymphocytes of infected humans is accelerated in a heterologous coculture system. Antibodies against gamma interferon (IFN-γ) are able to suppress most of the inhibitory activity, suggesting that IFN-γ is the dominant component.     

The longest, regular polypeptide 3(10) helix at atomic resolution

A synthetic, terminally blocked homodecapeptide from the C alpha, alpha-dimethylated glycyl residue alpha-aminoisobutyric acid has been analyzed by single-crystal X-ray diffraction and the structure refined to R = 0.073. The compound crystallizes as a perfect 3(10) helix, stabilized by eight consecutive intramolecular N-H . . . O = C hydrogen bonds. This is the first observation at atomic resolution of a regular polypeptide 3(10) helix as long as three complete turns.     

Predation on Ceriodaphnia cornuta and Brachionus calyciflorus by two Mesocyclops species coexisting in Barra Bonita reservoir (SP,Brazil)

Feeding experiments with two species of carnivorous copepod, Mesocyclops longisetus (Thiebaud) and Mesocyclops kieferi Van de Velde from Barra Bonita, a eutrophic reservoir in São Paulo, Brasil, were performed using two common types of prey: Ceriodaphnia cornuta, a cladoceran, with a mean body length of 464 µm (including spines) or 393 µm (without spines), and Brachionus calyciflorus, a rotifer with a mean body length of 350 µm (including spines) or 279 µm (without spines).Both species showed higher consumption rates on Brachionus than on Ceriodaphnia. For Mesocyclops longisetus, the average rates were: 2.19 prey ind^–1 h^–1 (Brachionus), and 1.30 prey ind^–1 h^–1 (Ceriodaphnia). For Mesocyclops kieferi, the rates were 1.85 prey ind^–1 h^–1 (Brachionus) and 0.60 prey ind^–1 h^–1 (Ceriodaphnia). These experimental data are discussed with reference to the dynamics of the predator and prey populations in the reservoir.Laboratorio de Limnologia, Departamento de Ciencias Biologicas, Universidade Federal de São CarlosCentro de Recursos Hidricos e Ecologia Aplicada Lab. de Limnologia, Departamento de Hidraulica e Saneamento, Escola de Engenharia de São Carlos, Universidade de São Paulo     

Linear oligopeptides: peptaibol antibiotics — preferred conformation of the 2–9 segment of emerimicins III and IV and all related short sequences

With the aim of obtaining information on the effect induced by main-chain length and amino acid sequence on the type of helical structure adopted by naturally-occurring peptides rich in C^α,α-dialkylated residues, an infrared absorption and ¹H nuclear magnetic resonance analysis of chloroform solutions of the protected 2–9 segment of the peptaibol antibiotics emerimicins III and IV,-(Aib)₃-l-Val-Gly-l-Leu-(Aib)₂-, and all related short sequences starting from both the N- and C-termini was performed. The results are consistent with the presence of folded structures of the β-bend type (in the shorter peptides) or 3₁₀-helices (in the longer peptides). Extent of formation and stability of the inter- and intramolecular H-bonds have been assessed as a function of concentration, temperature, addition of dimethylsulphoxide (DMSO) and the free radical 2,2,6,6-tetramethy-1-piperidinyloxy (TEMPO). At high peptide concentration both folded and helical structures tend to self-associate extensively. In the self-association process the N(1)H and N(2)H groups are those acting as H-bonding donors. These results agree well with those obtained in the solid state by X-ray diffraction on the octapeptide itself and selected short sequences.     

Alpha-beta-dehydro-amino acid residues in the design of peptide structures. Molecular and crystal structures of two folded dehydro peptides.

The molecular and crystal structures of two N alpha-protected tripeptide amides, containing in the central position the alpha-beta-dehydro-amino acid residue delta Phe (Z-configurational isomer), were determined by X-ray diffraction. While Z-Gly-delta Phez-L-Pro-NH2 is characterized in the crystal state by the presence of a type I beta-bend conformation (at the delta Phez-L-Pro sequence), Z-D-Ala-delta Phez-Gly-NH2 is folded into two consecutive beta-bends (type II' followed by type I), at the D-Ala-delta Phez and delta Phez-Gly sequences, respectively. In both cases the achiral delta Phez residue adopts a set of phi, psi angles typical of the right-handed helical conformation. The delta Phe residue may be exploited to design aromatic peptides with preferred secondary structures.     

The polypeptide 310-helix as a template and a spacer

Summary X-ray diffraction analyses have provided detailed structural information on the 3₁₀-helices of (i) pBrBz-d-(Me)Phe-(Aib)₂-d-(Me)Phe-Aib-OtBu and Ac-(Aib)₂-l-Lys(Bz)-(Aib)₂-l-Lys(Bz)-(Aib)₂-NHMe as suitable templates for molecular recognition studies, and (ii) pBrBz-TOAC-(l-Ala)₂-TOAC-l-Ala-NHtBu as an appropriate spacer for an ESR study of side chain to side chain interactions. In addition, in Ac-TOAC-(Aib)₂-l-Trp-Aib-OMe, forming a 3₁₀-helix, the TOAC residue plays the role of an effective quencher of the fluorescence of the tryptophan residue located one turn apart.     

Folding versatility of the C-terminal tetrapeptide amide sequence of the lipopeptaibol antibiotics trichodecenin and trichogin

Summary An X-ray diffraction analysis ofZ-l-Leu-Aib-Gly-l-Ile-l-Leu-OMe, containing the N-acylated tetrapeptide amide sequence-l-Leu-Aib-Gly-l-Ile-, showed that in the crystal state the carbonyl group preceding thel-Leu¹ residue acts as the acceptor of two C=OH–N intramolecular H-bonds, which give rise to an-l-Leu¹-Aib²-type-III' -turn and an-l-Leu¹-Aib²-Gly³-l-Ile⁴--turn, respectively. A second (type-I') -turn encompasses the-Aib²-Gly³-sequence. This is the third type of folding motif known for that tetrapeptide sequence, considering also those already published for the C-terminal segment of the lipopeptaibol antibiotics trichodecenin I and trichogin A IV.     

Crystallographic structure of a helical lipopeptaibol antibiotic analogue

An X-ray diffraction analysis of the [Fmoc⁰,TOAC^4,8, Leu-OMe¹¹] analogue of thelipopeptaibol antibiotic trichogin A IV shows that the undecapeptide isfolded in a right-handed, mixed /3₁₀-helix. The helicalmolecules are connected in a head-to-tail arrangement along the b-axisthrough C=O···H-N intermolecular H-bonding. Thispacking mode generates a hydrophobic cavity where the FmocN-protecting groups are accommodated. The distances andangles between the nitroxide groups of the two TOAC residues, separated byone turn of the -helix, have been determined.