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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

Our proposed experiments included: (1) immunzing mice with synthetic peptides; (2) preparing spleen and lymph node cells; (3) growing them under conventional conditions as well as in the rotatory vessel in appropriate medium reconstituting with synthetic peptides and/or cytokines as needed; and (4) comparing at regular time intervals the specific CTL activity as well as helper T-cell activity (in terms of both proliferative responses and cytokine production) using established procedures in my laboratory. We further proposed that once we demonstrated the merit of rotatory vessel technology to achieve desired results, these studies would be expanded to include immune cells from non-human primates (rhesus monkeys and chimpanzees) and also humans. We conducted a number of experiments to determine CTL induction by the synthetic peptides corresponding to antigenic proteins in HIV and HPV in different mouse strains that express MHC haplotypes H-2b or H-2d. We immunized mice with 100 ug of the synthetic peptide, suspended in sterile water, and emulsified in CFA (1:1). The immune lymph node cells obtained after 7 days were restimulated by culturing in T25 flask, HARV-10, or STLV-50, in the presence of the peptide at 20 ug/ml. The results from the 5'Cr-release assay consistently revealed complete abrogation of CTL activity of cells grown in the bioreactors (both HARV and STLV), while significant antigen-specific CTL activity was observed with cells cultured in tissue culture flasks. Thus, overall the data we generated in this study proved the usefulness of the NASA-developed developed technology for understanding the known immune deficiency during space travel. Additionally, this ex vivo microgravity technology since it mimics effectively the in vivo situation, it is also useful in understanding immune disorders in general. Thus, our proposed studies in TMC-NASA contract round II application benefit from data generated in this TMC-NASA contract round I study.

Sastry, Jagannadha K.↗
NASA NTRS1996

Template-Directed Ligation of Peptides to Oligonucleotides

Synthetic oligonucleotides and peptides have enjoyed a wide range of applications in both biology and chemistry. As a consequence, oligonucleotide-peptide conjugates have received considerable attention, most notably in the development of antisense constructs with improved pharmacological properties. In addition, oligonucleotide-peptide conjugates have been used as molecular tags, in the assembly of supramolecular arrays and in the construction of encoded combinatorial libraries. To make these chimeric molecules more accessible for a broad range of investigations, we sought to develop a facile method for joining fully deprotected oligonucleotides and peptides through a stable amide bond linkage. Furthermore, we wished to make this ligation reaction addressable, enabling one to direct the ligation of specific oligonucleotide and peptide components.To confer specificity and accelerate the rate of the reaction, the ligation process was designed to be dependent on the presence of a complementary oligonucleotide template.

Bruick, Richard K.↗
DOE OSTI2026

Peptide‐Induced Ferroelectricity in Charge‐Transfer Supramolecular Materials

Organic ferroelectrics are of great interest in sustainable energy conversion, information storage, flexible electronics, and potential biomedical applications as soft implants, among many other applications. Despite their broad potential, the development of organic ferroelectrics has remained limited, with only a few known examples in solid-state systems, primarily due to the lack of well-established design strategies compared to inorganic systems. Bio-inspired supramolecular chemistry offers a path to create functional nanostructures that are water-processable and biocompatible. We report here on supramolecular charge transfer (CT) systems in which peptides are covalently linked to dyads of electron-donating and electron-accepting moieties, creating amphiphiles that self-assemble into nanoscale ribbons in water. The peptide chirality-induced symmetry breaking in these crystalline nanostructures not only results in second harmonic activity but also generates ferroelectric behavior across multiple CT systems, demonstrating a versatile supramolecular approach to the design of new organic ferroelectrics. Furthermore, culturing primary neuron cells on coatings of the ferroelectric materials promoted axonal growth and enhanced action potentials, indicating improved neuronal maturity facilitated by the polar structure of the ferroelectric nanomaterials. The supramolecular strategy used here holds promise to create new water-processable ferroelectric biomaterials, opening avenues for innovative applications in cell charge transfer, neuronal axon growth, peptide symmetry breaking, self-assembling peptides, supramolecular ferroelectrics, proliferation, and bioelectronics.

charge transfer↗
DOE OSTI2024

Enhanced rare earth element recovery with cross-linked glutaraldehyde-lanthanide binding peptides in foam-based separations

Lanthanide Binding Tag (LBT) peptides that coordinate selectively with lanthanide ions can be used to replace the energy intensive processes used for the separation of rare earth elements (REEs). These surface-active biomolecules, once selectively complexed with the trivalent REE cations, can adsorb to air/aqueous interfaces of bubbles for foam-based REEs recovery. Glutaraldehyde, an organic compound that is a homobifunctional crosslinker for proteins and peptides, can be used to enhance the adsorption and interfacial stabilization of lanthanide-bound peptides films. The stability of the interfacial cross-linked films was tested by measuring their dilational and shear surface rheological properties. Surface activity of the adsorbed species was analyzed using pendant drop tensiometry, while surface density and molecular arrangement were determined using x-ray reflectivity and x-ray fluorescence near total reflection. Glutaraldehyde cross-linked REE-peptide complexes enhance the adsorption of lanthanides to air-water interfaces, resulting in thicker interfacial structures. Subsequently, these thicker layers enhance the dilational and shear interfacial rheological properties. The interfacial film stabilization and REEs extraction promoted by the cross-linker presented in this work provides an approach to integrate glutaraldehyde as a substitute of common foam stabilizers such as polymers, surfactants, and particles to optimize the recovery of REEs when using biomolecules as extractants.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Antimicrobial Peptides Can Facilitate Whole Blood Safety from Bacteria: A Proof of Concept

With continuous improvements to blood donor deferrals and the availability of sensitive tests for donation screening for infectious agents, bacterial contamination of whole blood (WB) and blood components stored for transfusion is a rare event. Nonetheless, it still occurs and remains a transfusion-associated risk in terms of septic transfusion reactions (STRs) and transfusion-transmitted bacterial infections with morbidity and mortality outcomes. One of the risk mitigation strategies for bacterial contamination is to implement treatment with currently available proactive pathogen reduction technologies (PRTs) for these transfusion products. Here, as a proof of concept, we tested two recently developed unique cationic antimicrobial peptides (AMPs; D-CONGA and D-CONGA-Q7) for WB safety from bacterial contamination. In this study, WB was inoculated with Escherichia coli and Staphylococcus epidermidis and treated with the two peptides to evaluate their bactericidal efficacy. The results demonstrated that D-CONGA and D-CONGA-Q7 exhibit potent inhibitory activity against the bacteria with a minimal inhibitory concentration (MIC) range of 4–8 and 1–8 μM, respectively, depending on the bacterial species tested. Time-kill kinetics further confirmed that the peptides exhibit bactericidal efficacy at 8 μM by achieving a 5-log 10 reduction (99.999%) of the bacterial load in WB with a time-dependent killing profile. Furthermore, even at 20 μM, the AMPs did not negatively impact hemolysis or hemostatic properties. We have further demonstrated using a cationic exchange resin that the cationic AMPs can be separated and removed from WB after the peptide treatments. During 35-day WB storage at 2–8 °C, 4 μM D-CONGA-Q7 one-time treatment prevented S. epidermidis growth and preserved WB quality and integrity. Overall, the results described here provide the first proof of concept that certain AMPs, such as D-CONGA and D-CONGA-Q7, can facilitate WB safety from bacteria during storage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Supramolecular Assembly of Lanthanide-Binding Tag Peptides for Aqueous Separation of Rare Earth Elements

Selective and eco-friendly separation and purification methods for rare earth elements (REEs) are necessary to meet the increasing demand for these valuable metals, which are extensively used in modern electronics and clean energy technologies. Mining feedstocks consist of REE mixtures as stable trivalent cations (Ln 3+ ) that are difficult to separate due to their identical charge and similar size. Lanthanide-binding tags (LBTs), peptide chelates that coordinate Ln 3+ in binding pockets, show promise as selective, high-affinity extractants. We demonstrate that the LBT variant LBTLLA 5– , designed for high selectivity for Tb 3+ , is an effective extractant, forming complexes with REEs in solution that subsequently organize into self-assembling structures rich in Ln 3+ . These structures condense into aggregates that can be separated, enabling an efficient, all-aqueous, eco-friendly separation process. The self-assembled structures are studied using dynamic light scattering, ζ-potential measurements, transmission electron microscopy, anomalous small-angle X-ray scattering, inductively coupled plasma optical emission spectroscopy, and ultraviolet–visible absorption spectroscopy, which confirm LBTLLA 5– peptide-REE ion binding and the further assembly of micron-scale structures rich in REEs. Molecular dynamics simulations reveal the interactions promoting aggregation as well as the integrity of the binding pocket upon self-assembly. We find that LBTLLA 5– :Ln 3+ complexes recruit excess cations within the macrostructures, and we demonstrate that aggregation and selective separation can be controlled by manipulating the metal-peptide ratio in solution. Furthermore, we demonstrate separation from equimolar mixtures of REE pairs Tb 3+ -Lu 3+ and Tb 3+ -La 3+ , supporting the application of LBT peptides as a platform for the selective separation of REEs.

LBT peptides↗
DOE OSTI2025

How short peptides disassemble tau fibrils in Alzheimer’s disease

Reducing fibrous aggregates of the protein tau is a possible strategy for halting the progression of Alzheimer’s disease (AD). Previously, we found that in vitro, the d-enantiomeric peptide (D-peptide) D-TLKIVWC disassembles ultra-stable tau fibrils extracted from the autopsied brains of individuals with AD (hereafter, these tau fibrils are referred to as AD-tau) into benign segments, with no energy source other than ambient thermal agitation. To consider D-peptide-mediated disassembly as a potential route to therapeutics for AD, it is essential to understand the mechanism and energy source of the disassembly action. Here, in this work, we show that the assembly of D-peptides into amyloid-like (‘mock-amyloid’) fibrils is essential for AD-tau disassembly. These mock-amyloid fibrils have a right-handed twist but are constrained to adopt a left-handed twist when templated in complex with AD-tau. The release of strain that accompanies the conversion of left-twisted to right-twisted, relaxed mock-amyloid produces a torque that is sufficient to break the local hydrogen bonding between tau molecules, and leads to the fragmentation of AD-tau. This strain-relief mechanism seems to operate in other examples of amyloid fibril disassembly, and could inform the development of first-in-class therapeutics for amyloid diseases.

Alzheimer's disease↗
DOE OSTI2024

Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects

Abstract Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough—all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs’ C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence.

Huang, Weiping (ORCID:0000000273063550)↗
NASA NTRS1999

Characterization of Treefoil Peptide Genes in Iron-Ion or X-Irradiated Human Cells

The gastrointestinal (GI) tract is especially sensitive to ionizing radiation, probably because of its high rate of cell turn over. Most of the data in the literature concerns the histological/anatomical description of damage rather than functional studies. In fact, previous reports in humans have shown that, at doses of 2 Gy or more, functional abnormalities appear indicating that in radiation sensitive tissues the effects of radiation are not limited to cell death. GI functions are controlled in particular by GI peptides. One hypothesis is that ionizing radiation may modulate the synthesis and release of these peptides and consequently may contribute largely to abnormalities in GI function. However, no previous studies have been concerned with GI-specific gene expression in irradiated GI tissues. The family of human trefoil peptides comprises three members thus far, all of which are expressed in specific regions of the GI tract. In addition, two trefoil peptides, pS2 (TFFI) and HITF (TFF2) are expressed in breast tissue. Their exact function in GI and breast tissues is unclear but mucosal integrity, repair, mucin secretion and responsiveness to hormones have been shown. We recently isolated and characterized pS2 as a novel p53- and estrogen receptor-independent gene whose MRNA expression in several cells lines was found to be delayed 4 to 7 days after irradiation with X-rays, fission neutrons or 1 GeV/n Fe-ions. The aim of the present study was to determine whether pS2 and HITF have a similar induction kinetics in irradiated gastric and breast cell lines, and whether they have the phorbol ester (TPA) responsive element (TRE).

Balcer-Kubiczek, E. K.↗
NASA NTRS2001

Simulation of Peptides at Aqueous Interfaces

Behavior of peptides at water-membrane interfaces is of great interest in studies on cellular transport and signaling, membrane fusion, and the action of toxins and antibiotics. Many peptides, which exist in water only as random coils, can form sequence-dependent, ordered structures at aqueous interfaces, incorporate into membranes and self-assembly into functional units, such as simple ion channels. Multi -nanosecond molecular dynamics simulations have been carried out to study the mechanism and energetics of interfacial folding of both non-polar and amphiphilic peptides, their insertion into membranes and association into higher-order structures. The simulations indicate that peptides fold non-sequentially, often through a series of amphiphilic intermediates. They further incorporate into the membrane in a preferred direction as folded monomers, and only then aggregate into dimers and, possibly, further into "dimers of dimers".

Pohorille, Andrew↗
NASA NTRS1993

Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

NASA Discipline Regulatory Physiology↗
NASA NTRS2019

Emergence of Simple Ion Channels by Self-Assembly of Short Peptides

As protocells transitioned from structures bound by membranes made of simple amphiphiles, such as fatty acids, to structures containing phospholipid membranes, they became nearly impermeable to charged species. Yet, the ability to transport ions across membranes was vital to regulating cellular volume, pH homeostasis, generating energy and sensing the environment. For this reason, life evolved ion channels, protein structures surrounding water-filled pores in the membrane that facilitated ion transport. In contemporary cells, ion channels are complex protein assemblies. Could the same function be carried out, even if less efficiently and selectively, by much simpler peptides at the origins of life? To answer this question, we turned to trichogen (GAIV), an 11-residue peptide that was found to permeabilize membrane, causing leakage of the vesicle content including ions. Since GAIV is synthesized non-gnomically, it represents as excellent model for the earliest, poorly optimized channels. Understanding the mechanism by which short peptides, such as GAIV, mediate ion transport across membranes provides crucial information on the emergence, structure and the mechanism of action of the earliest ion channels. In this study, we used extensive molecular dynamics (MD) simulations to investigate directly spontaneous assembly of GAIV peptide and its structural dynamics, the formation of an induced water pore across the membrane and consequently ion conduction through the membrane.

Wei, Chenyu↗
NASA NTRS2023

Design of a Minimal di-Nickel Hydrogenase Peptide

The most ancient processes for energy production in the evolution of life involve the reversible oxidation of molecular hydrogen by hydrogenase. Extant hydrogenase enzymes are complex, comprising hundreds of amino acids and multiple cofactors. We designed a 13 amino acid nickel-binding peptide capable of robustly producing molecular hydrogen from protons under a wide variety of conditions. The peptide forms a di-nickel cluster structurally analogous to a Ni-Fe cluster in [NiFe]-hydrogenase and the Ni-Ni cluster in acetyl-CoA synthase (ACS), two ancient, extant proteins central to metabolism. These experimental results clearly demonstrate that modern enzymes, despite their enormous complexity, likely evolved from simple peptide precursors on early Earth. One Sentence Summary: Small metal-binding peptides were the likely precursors of modern enzymes.

Joshua A. Mancini↗
NASA NTRS2023

Bacillus Subtilis Engineered for Aerospace Medicine: A Platform for Off-Planet Production of Pharmaceutical Peptides

Biologics, such as pharmaceutical peptides, have notoriously short shelf lives, insufficient for long-duration space flight missions to the Moon or Mars. To enable the sustainable presence of humans on the Moon or Mars, we must develop methods for on-site production of pharmaceutical peptides in space, a concept we call the Astropharmacy. Here, we present a proof-of-concept for the first step needed: a low-mass system for pharmaceutical production designed to be stable in space. To demonstrate feasibility, we engineered strains of the space-hardy spore-forming bacterium, Bacillus subtilis, to secrete two pharmaceutical peptides important for astronaut health: teriparatide (an anabolic agent for combating osteoporosis) and filgrastim (an effective countermeasure for radiation-induced neutropenia). We found that the secretion peptides from the walM and yoqH genes of B. subtilis worked well for secreting teriparatide and filgrastim, respectively. In consideration of the Translational Research Institute for Space Health (TRISH) challenge to produce a dose equivalent in 24 h, dried spores of our engineered strains were used to produce 1 dose equivalent of teriparatide from a 2 mL culture and 1 dose equivalent of filgrastim from 52 mL of culture in 24 h. Further optimization of strain growth conditions, expression conditions, and promoter sequences should allow for higher production rates to be achieved. These strains provide the template for future optimization efforts and address the first step in the Astropharmacy, capable of on-site production, purification, and processing of biopharmaceutical compounds in platforms amenable for use in space.

Alec Vallota-Eastman↗
DOE OSTI2024

Alpha(v)beta(6) integrin-binding peptides and methods of use thereof

The present invention provides peptide conjugates that target an integrin such as α v β 6 integrin. In particular embodiments, the peptide conjugates comprise a moiety such as a PEG moiety, an imaging agent, or a therapeutic agent. The peptide conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue. Compositions and kits containing the peptide conjugates of the present invention are also provided herein.

Tang, Yng↗
DOE OSTI2025

Using Multiple Isotope-Labeled Infrared Spectra for the Structural Characterization of an Intrinsically Disordered Peptide

Intrinsically disordered proteins (IDPs) rapidly interconvert between conformers, requiring an ensemble description. This complicates their experimental characterization, and force field limitations pose challenges for their simulation. Here, in this work, we use isotope-labeled and unlabeled infrared (IR) spectra to reweight simulated ensembles of the elastin-like peptide GVGVPGVG, a paradigmatic disordered peptide. By comparing the results obtained with different spectra, we explicitly show that the weights are underdetermined by the ensemble averaged data. We identify which labels and frequency regions maximize structural information while minimizing sensitivity to simulation error and show that these regions report on whether the peptide makes specific interactions. Our work shows the importance of incorporating simulations and simulated spectra at the planning stages of isotope-labeled IR experiments and more generally provides a framework for interpreting IR data for IDPs.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

A Copper-Binding Peptide with Therapeutic Potential against Alzheimer′s Disease: From the Blood–Brain Barrier to Metal Competition

Alzheimer’s disease (AD) is the most common form of dementia worldwide. AD brains are characterized by the accumulation of amyloid-β peptides (Aβ) that bind Cu 2+ and have been associated with several neurotoxic mechanisms. Although the use of copper chelators to prevent the formation of Cu 2+ -Aβ complexes has been proposed as a therapeutic strategy, recent studies show that copper is an important neuromodulator that is essential for a neuroprotective mechanism mediated by Cu 2+ binding to the cellular prion protein (PrPC). Therefore, in addition to metal selectivity and blood–brain barrier (BBB) permeability, an emerging challenge for copper chelators is to prevent the formation of neurotoxic Cu 2+ -Aβ species without perturbing the neuroprotective Cu 2+ -PrPC interaction. Previously, we reported the design of a tetrapeptide (TP) that withdraws Cu 2+ from Aβ(1–16) and impacts the Cu 2+ -induced aggregation of Aβ(1–40). In this study, we improved the drug-like properties of TP in a BBB model, evaluated the metal selectivity of the optimized peptide (TP*), and tested its effect on Cu 2+ coordination to PrPC and proteins involved in copper trafficking, such as copper transporter 1 and albumin. Our results show that changing the stereochemistry of the first residue prevents TP degradation in the BBB model and coadministration of TP with a peptide that increases BBB permeability allows its passage through the BBB model. TP* is highly selective toward Cu 2+ in the presence of Zn 2+ ions, transfers Cu 2+ to copper-trafficking proteins, and forms a ternary TP*-Cu 2+ -PrP species that does not perturb the physiological conformation of PrP and displays only a minor impact in the neuroprotective Cu 2+ -dependent interaction of PrPC with the N-methyl-d-aspartate receptor. Overall, these results show that TP* displays desirable features for a copper chelator with therapeutic potential against AD. Moreover, this is the first study that explores the effect of a Cu 2+ chelator with therapeutic potential for AD on Cu 2+ coordination to PrPC (an emerging key player in AD pathology), integrating recent knowledge about metalloproteins involved in AD with the design of copper chelators against AD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Shaping Peptide Assemblies Using Multifaceted Cyclic Tectons

Constructing distinct biomacromolecular assemblies typically necessitates target-specific selection and engineering of building blocks alongside optimization of assembly conditions. The challenge lies in achieving diverse morphological outcomes using simple, shared modules under identical conditions, a hallmark of natural systems that remains elusive in synthetic approaches. Here, in this work, we present a molecular scaffold-based strategy to instruct the coassembly of the same set of peptides into a variety of nanostructures across multiple dimensions. We create trifaceted cyclic scaffolds to manipulate two pairs of dimeric coiled-coil peptides prior to coassembly. These scaffolds, with addressable and orthogonal modules, allow controlled exposure of their cohesive faces, directing the formation of nanotriangles and fibrillar and lamellar assemblies. By tuning interpeptide arrangements that dictate scaffold geometry, we construct nonstraight fibrils with tunable curvature, which are rarely observed before. Notably, these scaffolds exhibit plasticity in adapting the sizes and orientations of cohesive faces to different assembly morphologies. The resultant nanostructures are consistent with the design and simulation results, demonstrating the reliability and predictability of this approach. Multifaceted cyclic scaffolds bridge the intellectual and physical gaps between building peptides and assemblies, holding promise for endowing various existing assembly systems with high tunability and versatility.

assembly morphology↗