Enantiomeric histidine-rich peptide coacervates enhance antigen delivery to T cells DOI
Ushasi Pramanik, Anirban Das, Elise M. Brown

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

SUMMARY Peptides and peptidomimetics that self-assemble via LLPS have recently emerged as building blocks for fabricating functional biomaterials due to their unique physicochemical properties dynamic nature. One of life’s most distinctive signatures is its selectivity chiral molecules and, date, coacervates comprised D-amino acids not been reported. Here, we demonstrate histidine-rich repeats (GHGXY) 4 (X=L/V/P) enantiomers undergo opening new avenues enhancing coacervate stability. Through a series biophysical studies, find kinetics, droplet size, fusion, encapsulation efficiency are dictated by the primary sequence. Further, these can encapsulate therapeutic cargo which then internalized endocytic mechanisms. Finally, show enhance antigen presentation CD4 + CD8 T cells resulting in robust proliferation production cytokines. Collectively, our study describes development characterization enantiomeric peptide attractive vaccine delivery vehicles with tunable properties. HIGHLIGHTS D amino acid-peptides were used first time construct phase separating Chirality does restrict or modulate other Antigen using enhances prolongs PROGRESS AND POTENTIAL self-assembly liquid-liquid separation (LLPS) result solute-rich serve biomaterials. Using repeats, this work demonstrates peptides composed entirely form coaceravtes. The kinetics bulk droplets be controlled through simple acid substitutions. coacervates, while immunologically inert, exert an adjuvanting effect leading cytokine production. materials showcased here possess high translational potential combined immunomodulators antigens against infectious diseases cancer. deliverables from will also inspire systems contribute knowledge cellular processes associated changes integral both physiology pathology.

Language: Английский

Determining the Multivalent Effects of d-Peptide-Based Radiotracers DOI Creative Commons
Siqi Zhang,

Xiaona Sun,

Wenhao Liu

et al.

Chemical & Biomedical Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Dextrorotary (d) peptides, composed of d-amino acids, are hyper-resistant to proteolytic hydrolysis, making them valuable ligands with excellent in vivo stability for radiopharmaceutical development. Multimerization is a well-established strategy enhancing the performance l-peptide-based radiopharmaceuticals. However, effect multimerization on fate d-peptide-based radiopharmaceuticals remains largely unexplored. Here, we synthesized d-peptide DPA, which targets PD-L1, along its dimer (DP2) and trimer (DP3). PET/CT imaging ex biodistribution studies were performed delineate pharmacokinetics target interactions [68Ga]DPA, [68Ga]DP2, [68Ga]DP3 both normal tumor-bearing mice. Our results revealed that tumor uptake kidney retention increased higher valency ([68Ga]DP3 > [68Ga]DP2 [68Ga]DPA). No significant differences observed liver, heart, lung, spleen, intestine, or bone among three radiotracers. Interestingly, reduction radioactivity bloodstream was detected [68Ga]DP3-treated group compared other two groups. Data analysis chiral configuration amino acids linking chemistry used dominant factors multimers. These findings indicate exerts distinct influence profiles l-peptide multimerization. This study deepens our understanding how mirror-imaged peptides/proteins interact living systems, paving way development harness d-peptides as targeting moieties.

Language: Английский

Citations

0
A fast and efficient virtual screening and identification strategy for helix peptide binders based on finDr webserver: A case study of bovine serum albumin (BSA) DOI

J. Bu,

Na Luo, Cheng Shen

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 141118 - 141118

Published: Feb. 1, 2025

Language: Английский

Citations

0
Thymidylate Kinase-Targeted Antimicrobial Peptides via Phage Display: A Novel Strategy against Gram-Negative Bacteria DOI
Mingyang Hu,

Yuwen Li,

Lu Zhao

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The rise of antimicrobial resistance (AMR) in Gram-negative bacteria, including Escherichia coli (E. coli), poses a major public health threat. This study aimed to address the limitations existing peptides (AMPs) by designing hybrid with enhanced targeting and antibacterial potency. Eight heptapeptide sequences were identified through phage display screening hybridized WP (WKKIWKPGIKKWIK), peptide exhibiting weak activity against bacteria. systematically evaluated for their activity, specificity, biocompatibility. SWP exhibited superior particularly E. K88 (TI = 2.378), demonstrated specific binding thymidylate kinase (TMK), key bacterial enzyme. In vivo studies employing mouse peritonitis model confirmed SWP's ability reduce loads mitigate tissue damage while maintaining excellent These findings underscore as promising candidate development targeted agents specificity stability pathogens.

Language: Английский

Citations

0
The hidden hand of molecular chirality in marine biogeochemistry DOI
Le Liu, Min Zhong, Quanrui Chen

et al.

Trends in Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Podoplanin-positive cell-derived small extracellular vesicles contribute to cardiac amyloidosis after myocardial infarction DOI Creative Commons
Maria Cimini, Ulrich H. E. Hansmann, Carolina González

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115408 - 115408

Published: March 1, 2025

Cardiac amyloidosis is a secondary phenomenon of an already pre-existing chronic condition. Whether cardiac represents one the complications post myocardial infarction (MI) has yet to be fully understood. Here, we show that occurs after MI and amyloid fibers are composed macrophage-derived serum A 3 (SAA3) monomers. SAA3 overproduction in macrophages triggered by exosomal communication from stromal cells (CSCs), which, response MI, activate expression platelet aggregation-inducing type I transmembrane glycoprotein, Podoplanin (PDPN). CSCPDPN+-derived small extracellular vesicles (sEVs) enriched SAA3, engages with macrophage Toll-like receptor 2, triggering consequent impaired clearance aggregation monomers into rigid fibers. deposits reduce contractility increase scar stiffness. Inhibition retro-inverso D-peptide, specifically designed bind monomers, prevents deposition fibrils improves heart function MI.

Language: Английский

Citations

0
Chiral Magnetic Memory Device at the 10 Nm Scale Using Self‐Assembly Nano Floret Electrodes DOI Creative Commons

Sebastian Reiß,

Salma Khaldi, Omer Shoseyov

et al.

Advanced Electronic Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract As data storage demands increase, the need for highly dense memory solutions becomes crucial. Magnetic nanostructures offer a pathway to achieve devices, but standard magnetic bit sizes are limited over 50 nm due fundamental ferromagnetic properties. In this study, 10 chiral device is introduced using self‐assembly gold nano‐floret device. The composed of SiGe nanowire with selectively decorated metallic shell deposited at tip. tip thiol linkers functions as weak ferromagnet particle that stabilized by ligands. high geometrical aspect ratio electrode measuring 30–60 in diameter and 1–10 microns length. mechanical contact Au counter Ti forms nanojunction can be probed electrically, bridging gap between nanoscale microscale. junction, molecules adsorbed together super‐paramagnetic iron oxide nanoparticles (SPIONs) forming same provides valuable insights into monolayer properties on selected metal surfaces demonstrating new approach characterizing molecular tilt angle monolayers molecules.

Language: Английский

Citations

0
Sensitivity to chirality correlates in a continuum with protein disorder DOI
Lucía B. Chemes, Lucı́a Álvarez

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Design and Synthesis of Monobody Variants with Low Immunogenicity DOI

Naoya Iwamoto,

Yukino Sato,

A. Manabe

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2023, Volume and Issue: 14(11), P. 1596 - 1601

Published: Oct. 9, 2023

Mirror-image proteins (d-proteins) are promising scaffolds for drug discovery because of their high proteolytic stability and low immunogenic properties. Facile reproducible processes the preparation functional d-proteins required application in therapeutic biologics. In this study, we designed synthesized a novel monobody variant with two cysteine substitutions that facilitate synthetic process via sequential native chemical ligations improve protein by disulfide bond formation. The anti-GFP model study exhibited good binding affinity to target enhanced green fluorescent protein. vivo administration (l-monobody) mice induced antidrug antibody (ADA) production, whereas no ADA production was observed following immunization mirror-image (d-monobody). These results suggest d-monobody is non-antibody scaffold

Language: Английский

Citations

9
Chemically Synthetic d-Sortase Enables Enzymatic Ligation of d-Peptides DOI
Ruichao Ding, Weiwei Shi, Ji‐Shen Zheng

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(26), P. 4857 - 4861

Published: June 26, 2023

We have described the chemical synthesis of d-Sortase A in large quantity and high purity by a hydrazide ligation strategy. The was fully active toward d-peptides D/L hybrid proteins, efficiency unaffected chirality C-terminus substrate. This study points using d-sortase as modern method for d-proteins proteins expands protein toolbox biotechnology.

Language: Английский

Citations

8
Roles of inter- and intramolecular tryptophan interactions in membrane-active proteins revealed by racemic protein crystallography DOI Creative Commons
Alexander J. Lander, Laura Domínguez Mercado, Xuefei Li

et al.

Communications Chemistry, Journal Year: 2023, Volume and Issue: 6(1)

Published: July 18, 2023

Tryptophan is frequently found on the surface of membrane-associated proteins that interact with lipid membrane. However, because their multifaceted interactions, it difficult to pinpoint structure-activity relationship each tryptophan residue. Here, we describe use racemic protein crystallography probe dedicated interactions a model tryptophan-rich bacteriocin aureocin A53 (AucA) by inclusion and/or exclusion potential ligands. In presence tetrahedral anions are isosteric head group phospholipids, distinct H-bond networks were revealed. donation W40 was critical for antibacterial activity, as its substitution 1-methyltryptophan resulted in substantial loss activity against bacterial clinical isolates. Meanwhile, ions revealed W3 partakes formation dimeric interface, thus suggesting AucA solution and dissociated phosphate Based these findings, could predict residue responsible well oligomeric state distant homologue lacticin Q (48%).

Language: Английский

Citations

8