Most aromatic foldamers adopt uniform secondary structures, offering limited potential for the exploration of conformational space and the formation of tertiary structures. Here we report the incorporation of spiro bis-lactams to allow controlled rotation of the backbone of an iteratively synthesised foldamer. This enables precise control of foldamer shape along two orthogonal directions, likened to the aeronautical yaw and roll axes. XRD, NMR and computational data suggest that homo-oligomers adopt an extended right-handed helix with a pitch of over 30 Å, approximately that of B-DNA. Compatibility with extant foldamers to form hetero-oligomers is demonstrated, allowing greater structural complexity and function in future hybrid foldamer designs.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110530 | PMC |
http://dx.doi.org/10.1038/s42004-023-00868-8 | DOI Listing |
Chem Biodivers
January 2025
Universidad Nacional de Tucuman Facultad de Bioquimica Quimica y Farmacia, Chemistry, Av. Kirchner 1900, 4000, San Miguel de Tucumán, ARGENTINA.
(Z)-3-butylamino-4,4,4-trifluoro-1-(2-hydroxyphenyl)but-2-en-1-one (1), a new β-aminoenone, has been investigated in terms of its intra- and intermolecular interactions. Vibrational, electronic and NMR spectroscopies were used for the characterization, while X-ray diffraction methods afforded the determination of the crystal structure. The compound is arranged in the crystal lattice as centre-symmetric H-bonded dimeric aggregates (C2/c monoclinic space group).
View Article and Find Full Text PDFPredicting reaction barriers for arbitrary configurations based on only a limited set of density functional theory (DFT) calculations would render the design of catalysts or the simulation of reactions within complex materials highly efficient. We here propose Gaussian process regression (GPR) as a method of choice if DFT calculations are limited to hundreds or thousands of barrier calculations. For the case of hydrogen atom transfer in proteins, an important reaction in chemistry and biology, we obtain a mean absolute error of 3.
View Article and Find Full Text PDFNat Chem
January 2025
Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.
View Article and Find Full Text PDFFood Chem
January 2025
State Key Laboratory of Food Science and Resources, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China; School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.
Vascular endothelial dysfunction is an important pathogenic factor in hypertension, in which angiotensin-converting enzyme (ACE) plays an important role. Peptides that bind to ACE may attenuate vascular endothelial dysfunction by altering the structure of ACE. This study demonstrated that ITAPHW and IRPNGL were resistant to simulated gastrointestinal fluid and were transported across the Caco-2 monolayer via the intercellular space, with ITAPHW showing a high apparent permeability coefficient of (1.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!