Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Angew Chem Int Ed Engl ; 63(2): e202316309, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38009917

RESUMO

Chirality is ubiquitous in nature, and homochirality is manifested in many biomolecules. Although ß-double helices are rare in peptides and proteins, they consist of alternating L- and D-amino acids. No peptide double helices with homochiral amino acids have been observed. Here, we report chiral ß-double helices constructed from γ-peptides consisting of alternating achiral (E)-α,ß-unsaturated 4,4-dimethyl γ-amino acids and chiral (E)-α,ß-unsaturated γ-amino acids in both single crystals and in solution. The two independent strands of the same peptide intertwine to form a ß-double helix structure, and it is stabilized by inter-strand hydrogen bonds. The peptides with chiral (E)-α,ß-unsaturated γ-amino acids derived from α-L-amino acids adopt a (P)-ß-double helix, whereas peptides consisting of (E)-α,ß-unsaturated γ-amino acids derived from α-D-amino acids adopt an (M)-ß-double helix conformation. The circular dichroism (CD) signature of the (P) and (M)-ß-double helices and the stability of these peptides at higher temperatures were examined. Furthermore, ion transport studies suggested that these peptides transport ions across membranes. Even though the structural analogy suggests that these new ß-double helices are structurally different from those of the α-peptide ß-double helices, they retain ion transport activity. The results reported here may open new avenues in the design of functional foldamers.


Assuntos
Aminoácidos , Peptídeos , Modelos Moleculares , Peptídeos/química , Aminoácidos/química , Conformação Proteica em alfa-Hélice , Ligação de Hidrogênio , Dicroísmo Circular
2.
RSC Med Chem ; 14(2): 332-340, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36846376

RESUMO

Directing Aß42 to adopt a conformation that is free from aggregation and cell toxicity is an attractive and viable strategy to design therapeutics for Alzheimer's disease. Over the years, extensive efforts have been made to disrupt the aggregation of Aß42 using various types of inhibitors but with limited success. Herein, we report the inhibition of aggregation of Aß42 and disintegration of matured fibrils of Aß42 into smaller assemblies by a 15-mer cationic amphiphilic peptide. The biophysical analysis comprising thioflavin T (ThT) mediated amyloid aggregation kinetic analysis, dynamic light scattering, ELISA, AFM, and TEM suggested that the peptide effectively disrupts Aß42 aggregation. The circular dichroism (CD) and 2D-NMR HSQC analysis reveal that upon interaction, the peptide induces a conformational change in Aß42 that is free from aggregation. Further, the cell assay experiments revealed that this peptide is non-toxic to cells and also rescues the cells from the toxicity of Aß42. Peptides with a shorter length displayed either weak or no inhibitory effect on Aß42 aggregation and cytotoxicity. These results suggest that the 15-residue cationic amphiphilic peptide reported here may serve as a potential therapeutic candidate for Alzheimer's disease.

3.
Chem Commun (Camb) ; 56(14): 2171-2173, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31970340

RESUMO

Unique ε-helical organizations (11-helices) from ß,γ-hybrid peptides composed of chiral ß3-amino acids along with achiral 3,3- or 4,4-dimethyl substituted γ-amino acids are disclosed.

4.
Chemistry ; 26(19): 4304-4309, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31960517

RESUMO

Due to their equivalent lengths, δ-amino acids can serve as surrogates of α-dipeptides. However, δ-amino acids with proteinogenic side chains have not been well studied because of synthetic difficulties and because of their insolubility in organic solvents. Recently we reported the spontaneous supramolecular gelation of δ-peptides composed of ß(O)-δ5 -amino acids. Here, we report the incorporation of ß(O)-δ5 -amino acids as guests into the host α-helix, α,γ-hybrid peptide 12-helix and their single-crystal conformations. In addition, we studied the solution conformations of hybrid peptides composed of 1:1 alternating α and ß(O)-δ5 -amino acids. In contrast to the control α-helix structures, the crystal structure of peptides with ß(O)-δ5 -amino acids exhibit α-helical conformations consisting of both 13- and 10-membered H-bonds. The α,δ-hybrid peptide adopted mixed 13/11-helix conformation in solution with alternating H-bond directionality. Crystal-structure analysis revealed that the α,γ4 -hybrid peptide accommodated the guest ß(O)-δ5 -amino acid without significant deviation to the overall helix folding. The results reported here emphasize that ß(O)-δ5 -amino acids with proteinogenic side chains can be accommodated into regular α-helix or 12-helix as guests without much deviation of the overall helix folding of the peptides.


Assuntos
Aminoácidos/química , Dipeptídeos/química , Peptídeos/química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares
5.
Chem Asian J ; 14(23): 4408-4414, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31670907

RESUMO

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.


Assuntos
Peptídeos/química , Ácidos Aminoisobutíricos/química , Cristalografia por Raios X , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice , Estereoisomerismo
6.
Chemistry ; 23(15): 3764-3772, 2017 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-28052426

RESUMO

Here, novel 12-helices in α,γ-hybrid peptides composed of achiral α-aminoisobutyric acid (Aib) and 4-aminoisocaproic acid (Aic, doubly homologated Aib) monomers in 1:1 alternation are reported. The 12-helices were indicated by solution and crystal structural analyses of tetra- and heptapeptides. Surprisingly, single crystals of the longer nonapeptide displayed two different helix types: the novel 12-helix and an unprecedented 15/17-helix. Quantum chemical calculations on both helix types in a series of continuously lengthened Aib/Aic-hybrid peptides confirm that the 12-helix is more stable than the 15/17-helix in shorter peptides, whereas the 15/17-helix is more stable in longer sequences. Thus, the coexistence of both helix types can be expected within a definite range of sequence lengths. The novel 15/17- and 12-helices in α,γ-hybrid peptides with 5→1 and 4→1 hydrogen-bonding patterns, respectively, can be viewed as backbone-expanded analogues of native α- and 310 -helices.


Assuntos
Ácido Aminocaproico/química , Ácidos Aminoisobutíricos/química , Peptídeos/química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Dobramento de Proteína , Estereoisomerismo
7.
Biopolymers ; 108(1)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27539268

RESUMO

Novel helical, structures unprecedented in the chemistry of α-polypeptides, may be found in polypeptides containing ß and γ amino acids. The structural characterization of C12 and C14 -helices in oligo ß-peptides was originally achieved using conformationally constrained cyclic ß-residues. This study explores the conformational characteristics of proteinogenic ß3 residues in homooligomeric sequences and addresses the issue of inducing a transition between C14 and C12 helices by the introduction of a guest α-residue. Folded C14 -helical structures are demonstrated for the nonapeptide Boc-[ß3 (R)Val]9 -OMe by NMR methods in CDCl3 -DMSO mixtures, while the peptide was found to be aggregated in CDCl3 . The insertion of a guest Aib residue into an oligo-ß-valine sequence in the octapeptide model Boc-[(ß3 (R)Val)3 -Aib-(ß3 (R)Val]4 -OMe results in well dispersed NH region in the NMR spectrum indicating folded structures in CDCl3 . Structure calculations for both the peptides using NOE distance constraints support a C14 helical structure in the homooligomer which transform into a C12 helix on introduction of the guest Aib residue.


Assuntos
Peptídeos/química , Valina/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Peptídeos/síntese química , Estrutura Secundária de Proteína , Solventes/química
8.
Chem Commun (Camb) ; 52(61): 9597-600, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27399170

RESUMO

We are reporting the influence of foldamer structures on their self-assembled architectures. In a sharp contrast to the ordered α,γ-hybrid 12-helix obtained from 1 : 1 alternating Aib and γ-Phe, the α,γ-hybrid peptides constituted with α-Phe and 4,4-dimethyl γ-amino acid (Aic) displayed the extended sheet type of conformations in solution and spontaneously self-assembled into thermally and proteolytically stable capsules. In contrast, the conformationally ordered 12-helix self-assembled into a three-dimensional supramolecular polyhedron.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...