Alfonso Bavoso

Structural versatility of peptides from Cα,α-dialkylated glycines: a conformational energy calculation and X-ray diffraction study of homopeptides from 1-aminocyclopentane-1-carboxylic acid☆

Abstract Coformational energy calculations on the 1-aminocyclopentane-1-carboxylic acid monopeptide Ac-Acc 5 -NHMe indicate that this C α,α -dialkylated, cyclic α-amino acid residue is conformationally restricted and that its minimum energy conformation falls in the α/3 10 -helical region. The results of the theoretical analysis are in agreement with the crystal-state structural tendency of p BrBz(Acc 5 ) 4 O t Bu·2 MeOH , p BrBz(Acc 5 ) 5 O t Bu· MeOH , and Z(Acc 5 ) 6 O t Bu, determined by X-ray diffraction and also described in this work (formation of 3 10 -helices). The implications for the use of Acc 5 residues in designing conformationally constrained analogues of bioactive peptides are briefly discussed.

Linear oligopeptides. Part 227. X-Ray crystal and molecular structures of two α-helix-forming (Aib-L-Ala)sequential oligopeptides, pBrBz-(Aib-L-Ala)5-OMe and pBrBz-(Aib-L-Ala)6-OMe

A crystal-state structutal analysis of pBrBz-(Aib-LAla)5-OMe tetrahydrate and pBrBz-(Aib-L-Ala)6-OMe dihydrate has been performed by X-ray diffraction. The decapeptide and dodecapeptide molecules are both basically α-helical with five and seven 1 â†� 5 intramolecular H-bonds, respectively. A similarity between the two structures is also seen near the C-terminus, where regularity of the α-helix is disrupted in favour of formation of intramolecular H-bonds of the 1 â†� 4 and 1 â†� 6 types. A brief comparison with parameters and interactions characteristic of the helices present in globular proteins has been made.

Long, Chiral Polypeptide 310-Helices at Atomic Resolution

The crystal-state preferred conformation of the terminally blocked hepta- and octapeptides with the general formula -(Aib)n L-Leu-(Aib)2- (n = 4 and 5, respectively), determined by X-ray diffraction, was found to be a right-handed 3(10)-helix stabilized by five and six consecutive intramolecular NH...O = C H-bonds of the C(10)-III type, respectively. The octapeptide structure represents the first observation at atomic resolution of a regular, chiral 3(10)-helix larger than two complete turns. In both cases the right handed screw sense of the helix is dictated by the presence of the single, internal L-residue. This study confirms the propensity of short peptides rich in Aib, the prototype of the amino acid residues dialkylated at the alpha carbon, to adopt a 3(10)-helical structure and is expected to help our understanding of the conformational preferences of the membrane-active, channel-forming, ion-transporting peptaibol antibiotics.

Structural versatility of peptides from Cα,α-dialkylated glycines: an infrared absorption and 1H n.m.r. study of homopeptides from 1-aminocyclopentane-1-carboxylic acid

Abstract The conformational preferences of terminally-blocked homopeptides of 1-aminocyclopentane-1-carboxylic acid from monomer to hexamer in chloroform solution were assessed by infrared absorption and 1 H nuclear magnetic resonance as a function of concentration, temperature, and addition of perturbing agents. The results obtained strongly support the view that an incipient 3 10 -helix is first formed at the tripeptide level. A comparison is made with the preferred conformation of homopeptides from the higher homologue 1-aminocyclohexane-1-carboxylic acid and the open chain analogue C α,α -diethylglycine.

Linear oligopeptides — effect of lengthening of the main chain by one tetrahedral carbon atom in the -Aib-l-Ala- sequence: a solid-state conformational analysis of segments of polypeptide antibiotics

Abstract The infrared absorption and X-ray diffraction conformational analysis of t-Boc-Aib- l -Ala-Aib-OMe have shown the presence of the type-1 4→1 intramolecularly H-bonded peptide conformation (β-bend) in the solid state. Lengthening of the chain by one tetrahedral carbon atom, as in t-Boc-Aib-βAla-Aib-OMe, has a disruptive effect on this folded structure. It has also been found that two water molecules co-crystallize with each molecule of the l -Ala containing tripeptide. These results are discussed in comparison with those, previously reported, obtained in chloroform solution.

Molecular Structure of Peptaibol Antibiotics: Solution Conformation and Crystal Structure of the Octapeptide Corresponding to the 2–9 Sequence of Emerimicins III and IV

The infrared absorption and 1H nuclear magnetic resonance analyses of chloroform solutions of the terminally-blocked segment corresponding to the 2-9 sequence of emerimicins III and IV, -(Aib)3-L-Val-Gly-L-Leu-(Aib)2-, are consistent with the presence of a 3(10)-helical structure of high thermal stability. The crystal structure of the octapeptide, obtained by X-ray diffraction indicates the formation of a right-handed 3(10)-helix, stabilized by six consecutive intramolecular N-H....O:C H-bonds, slightly distorted at the level of the L-Leu residue.

Linear oligopeptides. Part 147. Chemical and crystallographic study of the reaction between benzyloxycarbonyl chloride and α-aminoisobutyric acid

From the reaction mixture of benzyloxycarbonyl chloride and α-aminoisobutyric acid three crystalline compounds were isolated and characterized by chromatographic and spectroscopic techniques and X-ray diffraction. Two of them are polymorphic forms of the N-protected amino acid, which differ in the orientation of the phenyl ring relative to the urethane moiety and in the packing modes of the molecules, including the intermolecular hydrogen-bonding arrangements. The third compound is the N-protected dipeptide, the formation of which is not unexpected in the synthesis of the N-benzyloxycarbonyl amino acid derivative. The crystal structure of the symmetric carboxylic anhydride from the N-protected amino acid, a reasonable reactive intermediate in the formation of the N-protected dipeptide, is also described.

Cyclic peptide metal salt adducts. II. crystal structure of the silver nitrate cyclosarcosylsarcosine 2:1 adduct

Abstract The crystal structure analysis of the 2:1 adduct of cyclosarcosylsarcosine with silver(I) nitrate shows that the Ag(I) ion directly interacts with the carbonyl oxygen atoms of the peptide moiety. The independent unit is composed of a half cyclosarcosylsarcosine molecule, which sits on a crystallographic center of symmetry, per each silver nitrate unit. The crystal is held together by strong coulombic interactions between the silver and the nitrate ions and by ion- dipole interactions between the silver ion and the organic molecule. The coordination at the Ag(I) ion cannot be described in terms of a regular geometry; each silver ion experiences different types of contacts with the surrounding oxygen atoms. Six Ag-O interactions are in the fange 2.35-2.68 A; a seventh Ag-O interaction presents a distance of 2.90 A. This latter contact is perhaps the cause of the severe distortion from the ideal octahedral geometry observed experimentally. The nitrate ion and the cyclic peptide molecule are both nearly planar.

Preferred structures of constrained peptides from achiral α,α-dialkyiated glycyl residues with acyclic side chains

Conformational energy computations of the monopeptides from three achiral α,α-dialkylated glycyl residues with acyclic side chains (namely α,α-dimethyl-; α,α-diethyl-; and α, α-di-n-propylglycines) are reported as a function of the relevant N-Cα-C′ bond angle. In parallel, experimental studies were performed in the solid state (infrared absorption and X-ray diffraction) and in solution (infrared absorption and proton magnetic resonance) on the corresponding protected homo-peptide series (the former series to the dodecamer, the other two series to the pentamers). The results obtained unequivocally indicate that the preference from a helical to a fully extended conformation increases as side-chain bulkiness increases. The longest homo-peptides from α,α-dimethylglycine form stable 310-helices. A picture of the mode of self-association of the helical structures has also been determined. The results of the theoretical analyses fit well with the experimentally observed conformational properties in the solid state and in chloroform solution.

A hairpin-shaped peptide conformation stabilized by multiple intramolecular H-bonds for a linear alternating D,L hexapeptide

Abstract Sequential L,D polypeptides have been the object of investigations by many authors (1–4), since it was realized that they are strictly related to a natural occurring peptide, gramicidin A, which forms monovalent cation selective transmembrane channels in biological membranes and lipid bilayers (5,6). Here we present the results obtained by x-ray analysis of a linear hexapeptide, Boc-(D-aIle-L-Ile)3-OMe, which, in the solid state, gives rise to a chain reversal stabilized by multiple intramolecular hydrogen bonds. It is the first description of a β-turn (C10) and an α-turn (C13) fused together and included in a larger 17-membered ring (C17) occurring in a linear peptide.