Conformations of Unsolvated Glycine-Based Peptides (original) (raw)
Related papers
Biopolymers, 1990
The preferred conformation of the Cα,α-diphenylglycine residue was determined in simple derivatives and dipeptides. The dipeptides were synthesized by the 5(4H)-oxazolone (from the N-para-bromobenzoylated amino acid) method. This activated intermediate and a reaction by-product, para-bromobenzoylbenzhydrylamine, were characterized inter alia by x-ray diffraction. Conformational energy calculations on the Cα,α-diphenylglycine mono-peptide, Ac-Døg-NHMe, indicate that this Cα,α-symmetrically disubstituted residue is conformationally restricted and that its minimum energy conformation falls in the fully extended (C5) region. The results of the theoretical analysis are in agreement with the solution and crystal-state structural tendency of mClAc-Døg-OH, Z-Døg-OtBu, pBrBz-Døg-Gly-OMe and its tert-butyl ester analogue, determined by ir absorption, lH-nmr, and x-ray diffraction, and also described in this work. The implications for the use of the Døg residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.
Preferred conformation of peptides rich in Ac8c, a medium-ring alicyclic Cα,α-disubstituted glycine
Journal of Peptide Science, 1996
A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C"'"-disubstituted glycine 1 -aminocyclooctane-1 -earboxylic acid (Acec), and two Ala/Ac8c Mpeptides, were synthesized by solution methods and fully characterfied. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 'H-NMR The molecular structures of the amino acid derivative Z-Ac8c-OH. the dipeptide pBrBz-(Ac&-OH and the tripeptide pBrBz-(Acec)3-OtBu were assessed in the crystal state by X-ray diikction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Acsc residue is an effective B-turn and helix former. A comparison is also made with the conformational preferences of a-aminoisobutyric acid, the prototype of C"'"-disubstituted &cines. and of the other members of the family of 1 -aminocycloakane-1 -earboxylic acids (Ac,,c, with n = 3, $7) investigated so far. The implications for the use of the Acsc residue in peptide conformational design are considered.
Preferred Conformation of Peptides Rich in Ac8c, a Medium-ring Alicyclic C,-disubstituted Glycine
J Pept Sci, 1996
A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C"'"-disubstituted glycine 1-aminocyclooctane-1-earboxylic acid (Acec), and two Ala/Ac8c Mpeptides, were synthesized by solution methods and fully characterfied. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 'H-NMR The molecular structures of the amino acid derivative Z-Ac8c-OH. the dipeptide pBrBz-(Ac&-OH and the tripeptide pBrBz-(Acec)3-OtBu were assessed in the crystal state by X-ray diikction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Acsc residue is an effective B-turn and helix former. A comparison is also made with the conformational preferences of a-aminoisobutyric acid, the prototype of C"'"-disubstituted &cines. and of the other members of the family of 1-aminocycloakane-1-earboxylic acids (Ac,,c, with n = 3, $7) investigated so far. The implications for the use of the Acsc residue in peptide conformational design are considered.
Macromolecules, 1993
The molecular structures of four protected isovaline-(Iva-)containing peptides to the pentamer level have been determined by x-ray diffraction. The peptides are t-Boc-Ala-( S ) -1va-Ala-OMe ( t-Boc : tert-butyloxycarbonyl; OMe : methoxy) and its ( R ) -1va diastereomer, and t-Boc-[ Ala-( R ) -Iva],-Ala-OH and its (S) -1va diastereomeric methyl ester analogue. The two tripeptides are folded in an open type I1 @-bend conformation. The fully developed right-handed 310-helix formed by the ( R ) -1va pentapeptide, which includes an unusual intramolecular (acid) 0 -H * . O=C(peptide) H bond, is partially unfolded (near the C-terminus) in the ( S ) -1va pentapeptide. 'H-nmr and Fourier transform ir absorption studies suggest that in CDCl, solution ( a ) the two tripeptides maintain a type I1 @-bend conformation of comparable stability and ( b ) both diastereomeric pentapeptide sequences adopt a fully developed 310-helix. A comparison with the preferred conformation of other extensively investigated C"."-disubstituted glycines is made and the implications for the use of the Iva residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.
Preferred conformation of peptides from C?,?-symmetrically disubstituted glycines: Aromatic residues
Biopolymers, 1991
The conformational preference of Cα,α-diphenylglycinc (Døg) and Cα,α-dibenzylglycine (Dbz) residues was assessed in selected derivatives and small peptides by conformational energy computations, ir absorption, 1H-nmr, and x-ray diffraction. Conformational energy computations on the two monopeptides strongly support the view that these Cα,α-symmetrically disubstituted glycines are conformationally restricted and that their minimum energy conformation falls in the fully extended (C5) region. The results of the theoretical analyses appear to be in agreement with the solution and crystal-state structural propensities of three derivatives and seven di-and tripeptides.
Macromolecules, 1993
The molecular structures of four protected isovaline-(Iva-)containing peptides to the pentamer level have been determined by x-ray diffraction. The peptides are t-Boc-Ala-( S ) -1va-Ala-OMe ( t-Boc : tert-butyloxycarbonyl; OMe : methoxy) and its ( R ) -1va diastereomer, and t-Boc-[ Ala-( R ) -Iva],-Ala-OH and its (S) -1va diastereomeric methyl ester analogue. The two tripeptides are folded in an open type I1 @-bend conformation. The fully developed right-handed 310-helix formed by the ( R ) -1va pentapeptide, which includes an unusual intramolecular (acid) 0 -H * . O=C(peptide) H bond, is partially unfolded (near the C-terminus) in the ( S ) -1va pentapeptide. 'H-nmr and Fourier transform ir absorption studies suggest that in CDCl, solution ( a ) the two tripeptides maintain a type I1 @-bend conformation of comparable stability and ( b ) both diastereomeric pentapeptide sequences adopt a fully developed 310-helix. A comparison with the preferred conformation of other extensively investigated C"."-disubstituted glycines is made and the implications for the use of the Iva residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.
Glycine in Water Favors the Polyproline II State
Biomolecules, 2020
Conformational preferences of amino acid residues in water are determined by the backbone and side-chain properties. Alanine is known for its high polyproline II (pPII) propensity. The question of relative contributions of the backbone and side chain to the conformational preferences of alanine and other amino acid residues in water is not fully resolved. Because glycine lacks a heavy-atom side chain, glycine-based peptides can be used to examine to which extent the backbone properties affect the conformational space. Here, we use published spectroscopic data for the central glycine residue of cationic triglycine in water to demonstrate that its conformational space is dominated by the pPII state. We assess three commonly used molecular dynamics (MD) force fields with respect to their ability to capture the conformational preferences of the central glycine residue in triglycine. We show that pPII is the mesostate that enables the functional backbone groups of the central residue to form the most hydrogen bonds with water. Our results indicate that the pPII propensity of the central glycine in GGG is comparable to that of alanine in GAG, implying that the water-backbone hydrogen bonding is responsible for the high pPII content of these residues.
Biopolymers, 1988
The conformational preferences of the N-trifluoroacetylated homo-peptides of Cα,α-diethylglycine from monomer to pentamer in chloroform solution were determined by using ir absorption and 1H-nmr. Intramolecular hydrogen bonding was found to be the dominant factor for all NH groups. The likely absence of a conformational transition upon increasing main-chain length, and the remarkable stability to dilution, heating, and addition of perturbing agents, are additional relevant findings of this study. These results are in agreement with those of the fully extended, C5-conformation-forming homo-peptides from the higher homolog Cα,α-di-n-propylglycine, but contrast dramatically to those of the homo-peptides from the lower homolog Cα,α-dimethylglycine, which have been shown to adopt the 310-helical structure.