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1.
JMIR Aging ; 7: e51675, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38599620

ABSTRACT

BACKGROUND: Digital technology is a social determinant of health that affects older people's ability to engage in health maintenance and disease prevention activities; connect with family and friends; and, more generally, age in place. Unfortunately, disparities in technology adoption and use exist among older adults compared with other age groups and are even greater among low-income older adults. OBJECTIVE: In this study, we described the development and implementation of a digital literacy training program designed with the dual goals of training low-income older adults in the community and teaching students about aging using a community-engaged learning (CEL) approach. METHODS: The training program was embedded within a 10-week CEL course that paired undergraduates (N=27) with low-income older adults (n=18) for 8 weeks of digital literacy training. Older adults and students met weekly at the local senior center for the training. Students also met in the classroom weekly to learn about aging and how to use design thinking to train their older adult trainees. Both older adults and students completed pre- and posttraining surveys. RESULTS: Older adults demonstrated increased digital literacy skills and confidence in the use of digital technology. Loneliness did not change from pre to postassessment measurements; however, older adults showed improvements in their attitudes toward their own aging and expressed enthusiasm for the training program. Although students' fear of older adults did not change, their comfort in working with older adults increased. Importantly, older adults and students expressed positive feelings about the trainee-trainer relationship that they formed during the training program. CONCLUSIONS: A CEL approach that brings together students and low-income older adults in the community has a strong potential to reduce the digital divide experienced by underserved older adults. Additional work is needed to explore the efficacy and scalability of this approach in terms of older adults' digital literacy as well as other potential benefits to both older and younger adults.


Subject(s)
Computer Literacy , Digital Technology , Poverty , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Learning , Poverty/psychology , Surveys and Questionnaires
2.
Appetite ; 188: 106632, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37307953

ABSTRACT

The ability to prepare meals at home is an important life skill with potential to improve dietary quality and reduce costs and thus may be particularly important for college students with food insecurity. However, heavy time demands, limited financial resources, and therefore other barriers such as lack of motivation to follow a healthy diet may constrain meal preparation skills. To gain greater insight into this issue, we conducted a mixed-methods study. The quantitative component assessed relationships among food security, motivation, and meal preparation skills. The qualitative component used focus groups to more closely consider college students' perceptions, values, and barriers surrounding preparing meals at home, including current practices, desired future practices, and the ways in which the campus could support their efforts. The survey (n = 226) assessed food security, meal preparation skills, and motivation (i.e., perceived ability and willingness) to consume a healthy diet. Ten focus groups (n = 60) discussed food choice, meal preparation practices, and ways in which the campus could help students develop meal preparation skills. Students with food insecurity had lower meal preparation skills and lower perceived ability to consume a healthy diet. However, a) willingness to consume a healthy diet and b) the impact of both willingness and perceived ability did not differ by food security status. Focus group data indicated that in-person and online cooking classes, information cards in the food pantry, and incentives (e.g., kitchen equipment and vouchers from local grocery stores) were popular ideas for improving home-meal preparation. A greater understanding of meal preparation skills and their interconnectedness to food choice and the campus environment may inform effective ways to support the ability and willingness of college students with food insecurity to prepare meals at home.


Subject(s)
Diet , Students , Humans , Meals , Food Preferences , Cooking , Food Supply , Food Insecurity
3.
Sci Rep ; 13(1): 7820, 2023 05 15.
Article in English | MEDLINE | ID: mdl-37188747

ABSTRACT

The vein pattern in insect wings allows this lightweight structure to carry multiple biological functions. Here, an investigation of the angular distribution of the vein struts in dragonfly wings revealed that the golden angle or golden ratio dominates the venation patterns. We find that the golden angle dominates the intervein angles in regions where thin veins and membranes demand strength reinforcement. A golden ratio partition method has thus been developed that explains a set of preferred intervein angles in distorted polygon-shaped venation cells throughout the venation pattern in dragonfly wings. These observations provide new evidence that the wing structure is spatially optimized, by the golden rule in nature, for supporting biomechanical functions of dragonfly wings.


Subject(s)
Odonata , Animals , Insecta , Veins , Wings, Animal/blood supply
4.
ACS Chem Neurosci ; 14(3): 378-388, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36651175

ABSTRACT

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of the amyloid ß (Aß) protein in blood vessels and leads to hemorrhages, strokes, and dementia in elderly individuals. Recent reports have shown elevated copper levels colocalized with vascular amyloid in human CAA and Alzheimer's disease patients, which have been suggested to contribute to cytotoxicity through the formation of reactive oxygen species. Here, we treated a transgenic rat model of CAA (rTg-DI) with the copper-specific chelator, tetrathiomolybdate (TTM), via intraperitoneal (IP) administration for 6 months to determine if it could lower copper content in vascular amyloid deposits and modify CAA pathology. Results showed that TTM treatment led to elevated Aß load in the hippocampus of the rTg-DI rats and increased microbleeds in the wild type (WT) animals. X-ray fluorescence microscopy was performed to image the distribution of copper and revealed a surprising increase in copper colocalized with Aß aggregates in TTM-treated rTg-DI rats. Unexpectedly, we also found an increase in the copper content in unaffected vessels of both rTg-DI and WT animals. These results show that IP administration of TTM was ineffective in removing copper from vascular Aß aggregates in vivo and increased the development of disease pathology in CAA.


Subject(s)
Alzheimer Disease , Cerebral Amyloid Angiopathy , Rats , Humans , Animals , Aged , Amyloid beta-Peptides/metabolism , Rats, Transgenic , Copper/metabolism , Chelation Therapy , Cerebral Amyloid Angiopathy/drug therapy , Cerebral Amyloid Angiopathy/metabolism , Alzheimer Disease/metabolism , Animals, Wild , Chelating Agents/pharmacology , Chelating Agents/metabolism , Brain/metabolism , Plaque, Amyloid/metabolism
6.
J Am Coll Health ; 71(6): 1639-1642, 2023.
Article in English | MEDLINE | ID: mdl-34314657

ABSTRACT

Objective:Food-insecure college students have expressed frustration toward their academic institution for failing to meet students' needs. However, it is unclear whether campus climate perceptions are related to food insecurity status. We examined the association between campus climate surrounding health and food insecurity status among college students.Participants:Participants were undergraduate students (n = 1378) enrolled at a public university.Methods:We used secondary data from the American College Health Association-National College Health Assessment II (ACHA-NCHA-II) with campus-specific measures of campus climate and food insecurity status.Results:Findings showed that students with less favorable views of campus climate were between 1.85 and 1.74 times more likely to be food insecure, even after adjusting for demographics and financial hardship.Conclusions:Future research is needed to better understand how students' campus climate perceptions can inform programs that effectively address food insecurity on college campuses.

7.
Metallomics ; 14(12)2022 12 08.
Article in English | MEDLINE | ID: mdl-36537552

ABSTRACT

X-ray fluorescence microscopy (XFM) has become a widely used technique for imaging the concentration and distribution of metal ions in cells and tissues. Recent advances in synchrotron sources, optics, and detectors have improved the spatial resolution of the technique to <10 nm with attogram detection sensitivity. However, to make XFM most beneficial for bioimaging-especially at the nanoscale-the metal ion distribution must be visualized within the subcellular context of the cell. Over the years, a number of approaches have been taken to develop X-ray-sensitive tags that permit the visualization of specific organelles or proteins using XFM. In this review, we examine the types of X-ray fluorophore used, including nanomaterials and metal ions, and the approaches used to incorporate the metal into their target binding site via antibodies, genetically encoded metal-binding peptides, affinity labeling, or cell-specific peptides. We evaluate their advantages and disadvantages, review the scientific findings, and discuss the needs for future development.


Subject(s)
Metals , Proteins , X-Rays , Metals/metabolism , Ions/metabolism , Microscopy, Fluorescence/methods
8.
ACS Omega ; 7(48): 43421-43431, 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36506191

ABSTRACT

Cryomicroscopy is commonly hampered by frost accumulation, reducing the visual clarity of the specimen. Pulling a vacuum or purging with nitrogen gas can greatly reduce the sample chamber's humidity, but at cryogenic temperatures, even minute concentrations of water vapor can still result in frost deposition. Here, a hygroscopic ice frame was created around the specimen to suppress frost growth during cryomicroscopy. Specifically, fluorescently tagged rat brain vessels were frozen on a silicon nitride window with an ice frame, and the luminescence of the fluorescent tag was improved by a factor of 6 compared to a similar specimen in only a nitrogen purge environment. These findings suggest that the simple implementation of a hygroscopic ice frame surrounding the specimen can substantially improve the visual clarity for cryomicroscopy, beyond that of a vacuum or nitrogen purge system.

9.
Nanoscale Adv ; 4(2): 573-581, 2022 Jan 18.
Article in English | MEDLINE | ID: mdl-36132685

ABSTRACT

Antimicrobial resistance (AMR) continues to threaten the effective treatment and prevention of bacterial infections. The spread of resistant infections is accelerated by the lack of fast and cost-effective tests for the detection of AMR at the point-of-care. We aimed to address this challenge by developing a diagnostic tool to detect one of the major forms of AMR, the ß-lactamase enzymes. Antibiotic-functionalized gold nanoparticles (AuNPs) have been successfully developed for the detection of ß-lactamases in challenging biological media, namely undiluted urine. Furthermore, these tools are compatible with samples containing a urine sample preservative (boric acid) or hematuria (blood). The functionalized AuNPs interact with the active ß-lactamases, resulting in the hydrolysis of the surface-bound antibiotics, which then inhibits binding of the AuNPs to a capture protein (a penicillin-binding protein) to indicate the presence of active ß-lactamases. We successfully integrated the antibiotic-functionalized AuNPs into a new lateral flow assay (LFA), which can be used to detect active ß-lactamases down to the detection limit of 11 nM. While we demonstrate the use of antibiotic-functionalized AuNPs in an LFA format to provide a novel method of detecting active ß-lactamases, these functionalized AuNPs are amenable to a range of alternative diagnostic technologies and could lead to vital point-of-care diagnostics for the early detection of multi-drug resistant infections.

10.
J Phys Chem Lett ; : 5341-5350, 2022 Jun 09.
Article in English | MEDLINE | ID: mdl-35678387

ABSTRACT

The solubilization of lipid membranes by Tween-20 is crucial for a number of biotechnological applications, but the mechanistic details remain elusive. Evidence from ensemble assays supports a solubilization model that encompasses surfactant association with the membrane and the release of mixed micelles to solution, but whether this process also involves intermediate transitions between regimes is unanswered. In search of mechanistic origins, increasing focus is placed on identifying Tween-20 interactions with controllable membrane mimetics. Here, we employed ultrasensitive biosensing approaches, including single-vesicle spectroscopy based on fluorescence and energy transfer from membrane-encapsulated molecules, to interrogate interactions between Tween-20 and submicrometer-sized vesicles below the optical diffraction limit. We discovered that Tween-20, even at concentrations below the critical micellar concentration, triggers stepwise and phase-dependent structural remodeling events, including permeabilization and swelling, in both freely diffusing and surface-tethered vesicles, highlighting the substantial impact the surfactant has on vesicle conformation and stability prior to lysis.

11.
Appetite ; 169: 105820, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34843752

ABSTRACT

Latinos have disproportionately high rates of diet-related diseases which are associated with acculturation to the U.S. This negative shift in dietary quality is paradoxical in light of gains in income and education that would be expected to lead to better diet. We examined the extent to which the dietary acculturation paradox among Mexican Americans can be explained by segmented assimilation, a theory that considers how immigrants' and their descendants' trajectories of integration are influenced by a complex interplay of individual, social, and structural factors. First, we performed confirmatory cluster analysis to identify three assimilation segments (classic, underclass, and selective) based on education, income, and an acculturation proxy derived from language, nativity, and time in the U.S. among Mexican-origin participants (N = 4475) of the 2007-2016 National Health and Nutrition Examination Survey (NHANES). These segments were then used as independent variables in linear regression models to estimate the relationship between cluster and dietary quality (assessed by the Health Eating Index (HEI)) and the interaction between cluster and gender, controlling for marital status. There were strong effects of cluster on dietary quality, consistent with hypotheses per segmented assimilation theory. The classic assimilation segment had the poorest diet, despite having higher income and education than the underclass segment. The selective segment had higher or similar dietary quality to the underclass segment. Consistent with expectations, this difference was driven by the relatively higher consumption of greens and beans and whole grains of those in the selective and underclass segments. Overall, women had better diets than men; however, the strongest gender contrast was in the underclass segment. This study advances understanding of dietary acculturation and potential disparities in diet-related health outcomes.


Subject(s)
Acculturation , Diet , Female , Hispanic or Latino , Humans , Male , Mexican Americans , Nutrition Surveys
12.
J Health Commun ; 26(7): 460-472, 2021 07 03.
Article in English | MEDLINE | ID: mdl-34304728

ABSTRACT

Guided by Uncertainty Management Theory, UMT, we tested a model that explicates how uncertainty arising from contradictory health information is managed through information seeking. In an online experiment, 763 U.S. adults were randomly assigned to one of three message conditions: contradictory, non-contradictory, or control. Participants in the contradictory and non-contradictory conditions answered questions about their perceptions of contradiction, issue and decision uncertainty, negative appraisals and emotions, and information-seeking intentions. They also completed measures of several moderator variables, including information overload, intolerance for uncertainty, and health self-efficacy. Baseline levels of issue and decision uncertainty were measured in the control condition. Model tenets were confirmed: perceptions of contradiction led to issue uncertainty which, in turn, prompted cognitive appraisals directly, and indirectly through increased decision uncertainty. The effects of issue and decision uncertainty on information-seeking intentions were mediated by negative appraisals and threat emotions. Individuals with high health self-efficacy and positive outcome expectations of information search were more likely to manage uncertainty through information seeking. These results support the use of the CHIP model when perceptions of contradiction and decision uncertainty need to be accounted for, while also validating UMT for its original purposes. Model refinements and implications are discussed.


Subject(s)
Emotions , Intention , Adult , Cognition , Humans , Self Efficacy , Uncertainty
13.
Front Public Health ; 9: 581497, 2021.
Article in English | MEDLINE | ID: mdl-33889557

ABSTRACT

Background: Past research suggests that knowledge supports- but strong illness expectations thwart- adoption of protective behaviors (e.g., handwashing). Strong illness expectations may place COVID-19 essential workers at risk. It is unclear, however, whether knowledge can moderate the negative effects of pessimistic illness expectations on protective behaviors. We test COVID-19 knowledge as a moderator of the effects of (1) pessimistic illness expectations and (2) essential worker status on adherence to protective behaviors. Methods: Participants (n = 350) completed measures of knowledge, illness expectations, and protective behaviors. We used chi-square tests to examine associations between variables and logistic regressions to test the moderation models predicting adherence (low, high) while controlling for demographics. Results: Knowledge, illness expectations, and adherence were significantly associated with each other (p < 0.05). Essential workers had stronger illness expectations and lower knowledge than did non-essential workers (p < 0.001). Logistic regressions showed a non-significant Worker Status × Knowledge interaction (p = 0.59) but a significant Knowledge × Illness Expectations interaction (p < 0.05) indicating that those with strong illness expectations and low knowledge were disproportionately at risk of failing to adhere to recommended behaviors. Conclusions: Knowledge promotes protective behaviors by buffering the negative effects of pessimistic illness expectations. Essential workers are more likely to have low levels of knowledge with strong illness expectations, suggesting that educational policies may be warranted.


Subject(s)
COVID-19/prevention & control , Communicable Disease Control , Guideline Adherence , Health Behavior , Adult , Aged , Female , Hand Disinfection , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Young Adult
14.
Gerontologist ; 61(7): 1131-1140, 2021 09 13.
Article in English | MEDLINE | ID: mdl-33103726

ABSTRACT

BACKGROUND AND OBJECTIVES: Scholars argue that volunteering enhances social, physical, and cognitive activities that are increasingly valued as people age, which in turn improves older adults' well-being via a host of psychosocial and neurobiological mechanisms. This study explicitly tested older adults' self-perceptions of aging as a mechanism underlying the mental health benefits of volunteering. RESEARCH DESIGN AND METHODS: Using 2-wave data from the Health and Retirement Study (2008/2010 for Wave 1 and 2012/2014 for Wave 2), we analyzed reports from a pooled sample of older adults aged 65 or older (N = 9,017). Participants reported on demographic characteristics, volunteer work (did not volunteer, 1-99 h/year, 100+ h/year), self-perceptions of aging, and depressive symptoms. We estimated an autoregressive cross-lagged panel model. RESULTS: Volunteering for 100 h or more per year was associated with older adults' more positive and less negative self-perceptions of aging in the subsequent wave (i.e., 4 years later), which in turn predicted fewer depressive symptoms. DISCUSSION AND IMPLICATIONS: This study suggests the promising role of volunteering in shaping older adults' self-perceptions of aging on a sustained basis and refines our understanding of the benefits volunteering brings. Findings shed light on future interventions aimed at improving older adults' adjustment to age-related changes and lessening ageism in society.


Subject(s)
Ageism , Mental Health , Aged , Aging , Humans , Self Concept , Volunteers
15.
Antibiotics (Basel) ; 9(10)2020 Sep 29.
Article in English | MEDLINE | ID: mdl-33003560

ABSTRACT

The misuse of antibiotics in health care has led to increasing levels of drug resistant infections (DRI's) occurring in the general population. Most technologies developed for the detection of DRI's typically focus on phenotyping or genotyping bacterial resistance rather than on the underlying cause and spread of DRI's; namely the misuse of antibiotics. An aptameric based assay has been developed for the monitoring of ampicillin in urine samples, for use in determining optimal antibiotic dosage and monitoring patient compliance with treatment. The fluorescently labelled aptamers were shown to perform optimally at pH 7, ideal for buffered clinical urine samples, with limits of detection as low as 20.6 nM, allowing for determination of ampicillin in urine in the clinically relevant range of concentrations (100 nM to 100 µM). As the assay requires incubation for only 1 h with a small sample volume, 50 to 150 µL, the test would fit within current healthcare pathways, simplifying the adoption of the technology.

16.
PLoS One ; 15(7): e0233029, 2020.
Article in English | MEDLINE | ID: mdl-32658927

ABSTRACT

BACKGROUND: Food insecurity, limited access to adequate food, in adulthood is associated with poor health outcomes that suggest a pattern of accelerated aging. However, little is known about factors that impact food insecurity in midlife which in turn could help to identify potential pathways of accelerated aging. METHODS: Low-income adults (n = 17,866; 2014 National Health Interview Survey), ages 18 to 84, completed a 10-item food security module and answered questions regarding health challenges (chronic conditions and functional limitations) and financial worry. We used multinomial logistic regression for complex samples to assess the association of health challenges and financial worry with food insecurity status and determine whether these associations differed by age group, while adjusting for poverty, sex, race/ethnicity, education, family structure, social security, and food assistance. RESULTS: Food insecurity rates were highest in late- (37.5%) and early- (36.0%) midlife, relative to younger (33.7%) and older (20.2%) age groups and, furthermore, age moderated the relationship between food insecurity and both risk factors (interaction p-values < .05, for both). The effects of poor health were stronger in midlife relative to younger and older ages. Unlike younger and older adults, however, adults in midlife showed high levels of food insecurity regardless of financial worry. CONCLUSIONS: Findings suggest that food insecurity in midlife may be more severe than previously thought. Greater efforts are needed to identify those at greatest risk and intervene early to slow premature aging.


Subject(s)
Food Supply/statistics & numerical data , Health Surveys/statistics & numerical data , Income , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Humans , Interviews as Topic , Male , Middle Aged , Risk Factors , Socioeconomic Factors , United States , Young Adult
17.
J Biol Chem ; 295(27): 8914-8927, 2020 07 03.
Article in English | MEDLINE | ID: mdl-32376688

ABSTRACT

Cerebral amyloid angiopathy (CAA) is a vascular disorder that primarily involves deposition of the 40-residue-long ß-amyloid peptide (Aß40) in and along small blood vessels of the brain. CAA is often associated with Alzheimer's disease (AD), which is characterized by amyloid plaques in the brain parenchyma enriched in the Aß42 peptide. Several recent studies have suggested a structural origin that underlies the differences between the vascular amyloid deposits in CAA and the parenchymal plaques in AD. We previously have found that amyloid fibrils in vascular amyloid contain antiparallel ß-sheet, whereas previous studies by other researchers have reported parallel ß-sheet in fibrils from parenchymal amyloid. Using X-ray fluorescence microscopy, here we found that copper strongly co-localizes with vascular amyloid in human sporadic CAA and familial Iowa-type CAA brains compared with control brain blood vessels lacking amyloid deposits. We show that binding of Cu(II) ions to antiparallel fibrils can block the conversion of these fibrils to the more stable parallel, in-register conformation and enhances their ability to serve as templates for seeded growth. These results provide an explanation for how thermodynamically less stable antiparallel fibrils may form amyloid in or on cerebral vessels by using Cu(II) as a structural cofactor.


Subject(s)
Amyloid beta-Peptides/metabolism , Cerebral Amyloid Angiopathy/metabolism , Copper/metabolism , Peptide Fragments/metabolism , Alzheimer Disease/metabolism , Amyloid/metabolism , Amyloid beta-Peptides/physiology , Brain/metabolism , Cerebral Amyloid Angiopathy/physiopathology , Humans , Magnetic Resonance Spectroscopy/methods , Microscopy, Atomic Force/methods , Molecular Conformation , Peptide Fragments/physiology , Plaque, Amyloid/metabolism , Protein Conformation, beta-Strand
18.
Metallomics ; 12(4): 539-546, 2020 04 01.
Article in English | MEDLINE | ID: mdl-32104807

ABSTRACT

Accumulation of fibrillar amyloid ß-protein (Aß) in parenchymal plaques and in blood vessels of the brain, the latter condition known as cerebral amyloid angiopathy (CAA), are hallmark pathologies of Alzheimer's disease (AD) and related disorders. Cerebral amyloid deposits have been reported to accumulate various metals, most notably copper and zinc. Here we show that, in human AD, copper is preferentially accumulated in amyloid-containing brain blood vessels compared to parenchymal amyloid plaques. In light of this observation, we evaluated the effects of reducing copper levels in Tg2576 mice, a transgenic model of AD amyloid pathologies. The copper chelator, tetrathiomolybdate (TTM), was administered to twelve month old Tg2576 mice for a period of five months. Copper chelation treatment significantly reduced both CAA and parenchymal plaque load in Tg2576 mice. Further, copper chelation reduced parenchymal plaque copper content but had no effect on CAA copper levels in this model. These findings indicate that copper is associated with both CAA deposits and parenchymal amyloid plaques in humans, but less in Tg2576 mice. TTM only reduces copper levels in plaques in Tg2576 mice. Reducing copper levels in the brain may beneficially lower amyloid pathologies associated with AD.


Subject(s)
Alzheimer Disease/prevention & control , Cerebral Amyloid Angiopathy/prevention & control , Copper/metabolism , Molybdenum/pharmacology , Parenchymal Tissue/drug effects , Plaque, Amyloid/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Brain/blood supply , Brain/drug effects , Brain/metabolism , Cerebral Amyloid Angiopathy/metabolism , Chelating Agents/pharmacology , Disease Models, Animal , Humans , Mice, Transgenic , Microscopy, Fluorescence/methods , Parenchymal Tissue/metabolism , Parenchymal Tissue/pathology , Plaque, Amyloid/metabolism
19.
J Am Chem Soc ; 142(5): 2145-2149, 2020 02 05.
Article in English | MEDLINE | ID: mdl-31923358

ABSTRACT

We report the application of lanthanide-binding tags (LBTs) for two- and three-dimensional X-ray imaging of individual proteins in cells with a sub-15 nm beam. The method combines encoded LBTs, which are tags of minimal size (ca. 15-20 amino acids) affording high-affinity lanthanide ion binding, and X-ray fluorescence microscopy (XFM). This approach enables visualization of LBT-tagged proteins while simultaneously measuring the elemental distribution in cells at a spatial resolution necessary for visualizing cell membranes and eukaryotic subcellular organelles.


Subject(s)
Imaging, Three-Dimensional/methods , Lanthanoid Series Elements/metabolism , Proteins/chemistry , Spectrometry, X-Ray Emission/methods , Amino Acid Sequence , Protein Binding
20.
RSC Adv ; 10(60): 36485-36494, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-35517937

ABSTRACT

Molecular probes typically require structural modifications to allow for the immobilisation or bioconjugation with a desired substrate but the effects of these changes are often not evaluated. Here, we set out to determine the effects of attaching functional handles to a first-generation cephalosporin. A series of cephalexin derivatives was prepared, equipped with chemical tethers suitable for the site-selective conjugation of antibiotics to functionalised surfaces. The tethers were positioned remotely from the ß-lactam ring to ensure minimal effect to the antibiotic's pharmacophore. Herein, the activity of the modified antibiotics was evaluated for binding to the therapeutic target, the penicillin binding proteins, and shown to maintain binding interactions. In addition, the deactivation of the modified drugs by four ß-lactamases (TEM-1, CTX-M-15, AmpC, NDM-1) was investigated and the effect of the tethers on the catalytic efficiencies determined. CTX-M-15 was found to favour hydrolysis of the parent antibiotic without a tether, whereas AmpC and NDM-1 were found to favour the modified analogues. Furthermore, the antimicrobial activity of the derivatives was evaluated to investigate the effect of the structural modifications on the antimicrobial activity of the parent drug, cephalexin.

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