Association of Diabetes with Changes in Blood Pressure during Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial.

INTRODUCTION: Diabetes mellitus is a common cause of kidney failure and is often complicated by autonomic neuropathy, which may have implications for blood pressure (BP) homeostasis during hemodialysis (HD). METHODS: In this post hoc analysis of the Frequent Hemodialysis Network (FHN) Daily Trial, we used random effects Poisson and linear regression models to estimate the association of diabetes (vs. not) with intra-dialytic hypotension (IDH) and peri-dialytic BP parameters, respectively. We tested for differential associations according to the randomized treatment (6/week vs. 3/week HD) and pre-HD systolic BP. RESULTS: Of the 244 patients with intra-dialytic BP data, 100 (41%) had diabetes at baseline. The mean age was 51 ± 14 years; overall, 39% were female. In adjusted models, diabetes (vs. not) was associated with a 93% higher risk of developing IDH (IRR: 1.93; 95% CI: 1.26, 2.95). There was no evidence that the randomized treatment assignment modified the association between diabetes and IDH (pinteraction = 0.32), but more potent associations were noted among those with higher pre-HD systolic BP (pinteraction < 0.001). Diabetes (vs. not) was associated with a lower adjusted nadir intra-HD BP (-4.2; 95% CI: -8.3, -0.2 mm Hg) but not with the pre- or post-HD systolic BP. CONCLUSIONS: Among participants of the FHN Daily Trial, patients with diabetes had a higher risk of IDH and lower nadir intra-HD systolic BP than patients without diabetes, even when undergoing HD up to 6 times per week.

Up-to-Date Colonoscopy Use in Asian and Hispanic Subgroups in New York City, 2003-2016.

BACKGROUND: Colorectal cancer screening uptake in the United States overall has increased, but racial/ethnic disparities persist and data on colonoscopy uptake by racial/ethnic subgroups are lacking. We sought to better characterize these trends and to identify predictors of colonoscopy uptake, particularly among Asian and Hispanic subgroups. STUDY: We used data from the New York City Community Health Survey to generate estimates of up-to-date colonoscopy use in Asian and Hispanic subgroups across 6 time periods spanning 2003-2016. For each subgroup, we calculated the percent change in colonoscopy uptake over the study period and the difference in uptake compared to non-Hispanic Whites in 2015-2016. We also used multivariable logistic regression to identify predictors of colonoscopy uptake. RESULTS: All racial and ethnic subgroups with reliable estimates saw a net increase in colonoscopy uptake between 2003 and 2016. In 2015-2016, compared with non-Hispanic Whites, Puerto Ricans, Dominicans, and Central/South Americans had higher colonoscopy uptake, whereas Chinese, Asian Indians, and Mexicans had lower uptake. On multivariable analysis, age, marital status, insurance status, primary care provider, receipt of flu vaccine, frequency of exercise, and smoking status were the most consistent predictors of colonoscopy uptake (≥4 time periods). CONCLUSIONS: We found significant variation in colonoscopy uptake among Asian and Hispanic subgroups. We also identified numerous demographic, socioeconomic, and health-related predictors of colonoscopy uptake. These findings highlight the importance of examining health disparities through the lens of disaggregated racial/ethnic subgroups and have the potential to inform future public health interventions.

Predictors of Colonoscopy Use Among Asian Indians in New York City, 2003 to 2016.

BACKGROUND: Asian Americans have the lowest colorectal cancer screening uptake of any racial and ethnic group in the United States. Asian Indians are among the most under-screened Asian American subgroups, but there is limited data for this population. We sought to characterize predictors of colonoscopy use among Asian Indians in New York City. METHODS: Using 2003 to 2016 data from the New York City Community Health Survey, we identified all Asian Indian participants aged 50 years or older. We examined the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 y) using logistic regression over 4 time periods: 2003 to 2008, 2009 to 2012, 2013 to 2014, 2015 to 2016. RESULTS: On multivariable analysis, language, age, income, recent exercise, body mass index, and influenza vaccination were associated with colonoscopy uptake in 1 time period. Compared with participants who preferred English, those who preferred an Indian language were less likely to have been up-to-date in 2013 to 2014 (odds ratio 0.12, 95% CI 0.02-0.66). Individuals older than 65 years were more likely than those aged 50 to 64 years to have received a colonoscopy in 2009 to 2012 (odds ratio 3.91, 95% CI 1.49-10.24), although the risk estimates were also consistently positive in the other 3 time periods. CONCLUSIONS: Among Asian Indians living in New York City, several demographic, socioeconomic, and health-related characteristics predict colonoscopy use. These findings highlight the importance of examining determinants of colonoscopy uptake in this understudied population to inform future public health interventions.

Factors Associated with Up-to-Date Colonoscopy Use Among Puerto Ricans in New York City, 2003-2016.

BACKGROUND: Colorectal cancer is the second leading cause of cancer death among Hispanic Americans. Puerto Ricans are the second largest Hispanic subgroup in the USA and the largest in New York City, but little is known about predictors of colorectal cancer screening uptake in this population. AIMS: We used the New York City Community Health Survey, a population-based telephone survey, to investigate predictors of up-to-date colonoscopy use over time among Puerto Ricans aged ≥ 50 years in NYC. METHODS: We assessed the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 years) using univariable and multivariable logistic regression over six time periods: 2003-2005, 2006-2008, 2009-2010, 2011-2012, 2013-2014, and 2015-2016. RESULTS: On multivariable analysis, age ≥ 65 years (OR 1.64-1.93 over three periods) and influenza vaccination (OR 1.86-2.17 over five periods) were the two factors most consistently associated with up-to-date colonoscopy use. Individuals without a primary care provider (OR 0.38-0.50 over three periods) and who did not exercise (OR 0.49-0.52 over two periods) were significantly less likely to have an up-to-date colonoscopy. CONCLUSIONS: Older age, influenza vaccination, having a primary care provider, and exercise are independent predictors of up-to-date colonoscopy use among Puerto Ricans in NYC. Interventions to improve screening colonoscopy uptake among Puerto Ricans should be targeted to those aged 50-64 years and who do not have a primary care provider.

Soft X-Ray and Cathodoluminescence Examination of a Tanzanian Graphite Deposit.

Hyperspectral soft X-ray emission (SXE) and cathodoluminescence (CL) spectrometry have been used to investigate a carbonaceous-rich geological deposit to understand the crystallinity and morphology of the carbon and the associated quartz. Panchromatic CL maps show both the growth of the quartz and the evidence of recrystallization. A fitted CL map reveals the distribution of Ti4+ within the grains and shows subtle growth zoning, together with radiation halos from 238U decay. The sensitivity of the SXE spectrometer to carbon, together with the anisotropic X-ray emission from highly orientated pyrolytic graphite, has enabled the C Kα peak shape to be used to measure the crystal orientation of individual graphite regions. Mapping has revealed that most grains are predominantly of a single orientation, and a number of graphite grains have been investigated to demonstrate the application of this new SXE technique. A peak fitting approach to analyzing the SXE spectra was developed to project the C Kα 2pz and 2p(x+y) orbital components of the graphite. The shape of these two end-member components is comparable to those produced by electron density of states calculations. The angular sensitivity of the SXE spectrometer has been shown to be comparable to that of electron backscatter diffraction.

Investigation of the Internal Structure of a Modern Seafloor Hydrothermal Chimney With a Combination of EBSD, EPMA, and XRD.

Samples from the sphalerite-dominated zone of a seafloor massive sulfide chimney, the Satanic Mills Chimney of the PACMANUS hydrothermal field, have been investigated to determine the internal macrostructure and microstructure of this zone, the phases present, and the distribution of metals. A combination of electron probe microanalysis, electron backscattered diffraction, and x-ray diffraction has been used. At the macroscale, this zone of the chimney wall is heavily porous and is comprised primarily of sphalerite, enclosing minor chalcopyrite, pyrite, and wurtzite. A Pb­As sulfosalt layer of possible microbial origins is present at the outer edge of the sphalerite matrix, next to a pore. The sphalerite has grown in globules on the order of 300 µm in diameter. At the microscale, the sphalerite features a colloform texture and a duplex-type grain structure consisting of either fine-grain regions in the center surrounded by coarse-grained regions or radiating coarse grains only. Pb- and As-rich bands have been detected in the colloform sphalerite, and growth twins have been observed in both the sphalerite and chalcopyrite crystals. A qualitative description of the growth of a typical globule is given, including nucleation, crystal growth, and solute redistribution.

Characteristics of methadone maintenance treatment patients prescribed opioid analgesics.

BACKGROUND: Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them with MMT patients not prescribed opioid analgesics. METHODS: We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012 to 2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients' report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-square tests, t tests, and Mann-Whitney U tests. RESULTS: Of 611 MMT patients, most reported chronic pain (62.0%), hepatitis C virus (HCV) infection (52.1%), and current use of illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 1.1-2.3) and chronic pain (aOR = 7.6, 95% CI: 4.6-12.6). CONCLUSION: Among MMT patients primarily in 3 Bronx clinics, nearly one third reported taking prescribed opioid analgesics. Compared with patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients.

Trajectories of Opioid Misuse and Opioid Use Disorder Among Adults With Chronic Pain and HIV: An Observational Study.

OBJECTIVES: In a longitudinal cohort of patients with HIV and chronic pain, we sought to (1) identify trajectories of opioid misuse and opioid use disorder (OUD) symptoms, and to (2) determine whether prescription opioid dose was associated with symptom trajectories. METHODS: We leveraged an existing 12-month longitudinal observational study, Project PIMENTO, of persons living with HIV and chronic pain who received care at a hospital system in the Bronx, New York. A quota sampling strategy was used to ensure variability of prescribed opioid use in the recruited sample. Research interviews occurred quarterly and assessed opioid behaviors and criteria for OUD. To describe symptom trajectories, we conducted 2 separate longitudinal latent class analyses to group participants into (1) opioid misuse and (2) OUD trajectories. Finally, we used multinomial logistic regression models to examine the relationship between baseline prescription opioid dose and symptom trajectories. RESULTS: Of 148 total participants, at baseline 63 (42.6%) had an active opioid prescription, 69 (46.6%) met the criteria for current opioid misuse, and 44 (29.7%) met the criteria for current OUD. We found 3 opioid misuse and 3 OUD symptom trajectories, none of which showed worsened symptoms over time. In addition, we found that higher prescription opioid dose at baseline was associated with a greater OUD symptom trajectory. CONCLUSIONS: Opioid misuse and OUD were common but stable or decreasing over time. Although these results are reassuring, our findings also support prior studies that high-dose opioid therapy is associated with greater OUD symptoms.

Incarceration history and opioid use among adults living with HIV and chronic pain: a secondary analysis of a prospective cohort study.

BACKGROUND: Adults living with HIV have disproportionately high chronic pain, prescription opioid use, history of substance use, and incarceration. While incarceration can have long-lasting health impacts, prior studies have not examined whether distant (>1 year prior) incarceration is associated with opioid use for chronic pain, or with opioid misuse or opioid use disorder among people living with HIV and chronic pain. METHODS: We conducted a secondary analysis of a prospective cohort study of adults living with HIV and chronic pain. The independent variables were any distant incarceration and drug-related distant incarceration (both dichotomous). Dependent variables were current long-term opioid therapy, current opioid misuse, and current opioid use disorder. A series of multivariate logistic regression models were conducted, adjusting for covariates. RESULTS: In a cohort of 148 participants, neither distant incarceration nor drug-related incarceration history were associated with current long-term opioid therapy. Distant incarceration was associated with current opioid misuse (AOR 3.28; 95% CI: 1.41-7.61) and current opioid use disorder (AOR 4.40; 95% CI: 1.54-12.56). Drug-related incarceration history was also associated with current opioid misuse (AOR 4.31; 95% CI: 1.53-12.17) and current opioid use disorder (AOR 7.28; 95% CI: 2.06-25.71). CONCLUSIONS: The positive associations of distant incarceration with current opioid misuse and current opioid use disorder could indicate a persistent relationship between incarceration and substance use in people living with HIV and chronic pain. Additional research on opioid use among formerly incarcerated individuals in chronic pain treatment is needed.

Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents.

Akt has emerged as a critical target for the development of anti-cancer therapies. It has been found to be amplified, overexpressed, or constitutively activated in numerous human malignancies with oncogenesis derived from the simultaneous promotion of cell survival and suppression of apoptosis. A valuable alternative to the more common ATP-mimetic based chemotherapies is a substrate-mimetic approach, which has the potential advantage of inherent specificity of the substrate-binding pocket. In this paper we present the development of high affinity non-peptidic, substrate-mimetic inhibitors based on the minimum GSK3beta substrate sequence. Optimization of initial peptidic leads resulted in the development of several classes of small molecule inhibitors, which have comparable potency to the initial peptidomimetics, while eliminating the remaining amino acid residues. We have identified the first non-peptidic substrate-mimetic lead inhibitors of Akt 29a-b, which have affinities of 17 and 12 microM, respectively. This strategy has potential to provide a useful set of molecular probes to assist in the validation of Akt as a potential target for anti-cancer drug design.

Patterns of diuretic use in the intensive care unit.

PURPOSE: To inform future outcomes research on diuretics, we sought to describe modern patterns of diuretic use in the intensive care unit (ICU), including diuretic type, combination, and dosing. We also investigated two possible quality improvement targets: furosemide dosing in renal impairment and inclusion of an initial bolus with continuous furosemide infusions. MATERIALS AND METHODS: In this descriptive study, we retrospectively studied 46,037 adult ICU admissions from a publicly available database of patients in an urban, academic medical center. RESULTS: Diuretics were employed in nearly half (49%, 22,569/46,037) of ICU admissions. Mechanical ventilation, a history of heart failure, and admission to the post-cardiac surgery unit were associated with a higher frequency of diuretic use. Combination use of different diuretic classes was uncommon. Patients with severely impaired kidney function were less likely to receive diuretics. Furosemide was by far the most common diuretic given and the initial intravenous dose was only 20 mg in more than half of ICU admissions. Among patients treated with a continuous infusion, 30% did not receive a bolus on the day of infusion initiation. CONCLUSIONS: Patterns of diuretic use varied by patient-specific factors and by ICU type. Diuretic dosing strategies may be suboptimal.

Design, synthesis, potency, and cytoselectivity of anticancer agents derived by parallel synthesis from alpha-aminosuberic acid.

Chemotherapy in the last century was characterized by cytotoxic drugs that did not discriminate between cancerous and normal cell types and were consequently accompanied by toxic side effects that were often dose limiting. The ability of differentiating agents to selectively kill cancer cells or transform them to a nonproliferating or normal phenotype could lead to cell- and tissue-specific drugs without the side effects of current cancer chemotherapeutics. This may be possible for a new generation of histone deacetylase inhibitors derived from amino acids. Structure-activity relationships are now reported for 43 compounds derived from 2-aminosuberic acid that kill a range of cancer cells, 26 being potent cytotoxins against MM96L melanoma cells (IC50 20 nM-1 microM), while 17 were between 5- and 60-fold more selective in killing MM96L melanoma cells versus normal (neonatal foreskin fibroblasts, NFF) cells. This represents a 10- to 100-fold increase in potency and up to a 10-fold higher selectivity over previously reported compounds derived from cysteine (J. Med. Chem. 2004, 47, 2984). Selectivity is also an underestimate, because the normal cells, NFF, are rarely all killed by the drugs that also induce selective blockade of the cell cycle for normal but not cancer cells. Selected compounds were tested against a panel of human cancer cell lines (melanomas, prostate, breast, ovarian, cervical, lung, and colon) and found to be both selective and potent cytotoxins (IC50 20 nM-1 microM). Compounds in this class typically inhibit human histone deacetylases, as evidenced by hyperacetylation of histones in both normal and cancer cells, induce expression of p21, and differentiate surviving cancer cells to a nonproliferating phenotype. These compounds may be valuable leads for the development of new chemotherapeutic agents.

Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites.

Third world nations require immediate access to inexpensive therapeutics to counter the high mortality inflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapies based on this recently validated antimalarial target. This novel series of compounds represents the first Plasmodium falciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitors displaying excellent in vitro activity (IC(50) < 1 nM) and toxicity to cultured parasites at low concentrations (ED(50) < 100 nM). Initial studies of absorption, metabolism, and oral bioavailability are reported.

Differential effects of Stat3 inhibition in sparse vs confluent normal and breast cancer cells.

The signal transducer and activator of transcription-3 (Stat3) is persistently activated in many cancers such as cancer of the breast and is required for transformation by a number of oncogenes. Signaling through Stat3 is determined by a key phosphorylation at tyr-705. We previously demonstrated that cell-to-cell adhesion brought about through cell aggregation or confluence of cultured cells causes a dramatic increase in Stat3 tyr705 phosphorylation and consequently Stat3 activity in both normal and tumor cells. To examine the role of Stat3 at specific time-points relative to confluence, we used two different approaches of Stat3 inhibition: (1). Introduction of high levels of peptide analogues, which block the Stat3-SH2 domain, to inhibit Stat3 binding to and phosphorylation by growth factor receptors. (2). Treatment with two platinum compounds which bind the Stat3 protein and inhibit its activity without affecting its phosphorylation directly. The results demonstrate that Stat3 downregulation in vSrc transformed NIH3T3 cells or in breast cancer lines harboring activated Src induces apoptosis, which is evident at all densities but is more pronounced at post-confluence. In normal cells on the other hand, Stat3 inhibition at post-confluence caused apoptosis while in sparsely growing cells it induced merely a growth retardation.

Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity.

The critical role of signal transducer and activator of transcription 3 (Stat3) in the growth and survival of human tumor cells identifies it as a promising target for cancer drug discovery. We previously identified a Stat3 SH2 domain-binding phosphopeptide, PY*LKTK, and its tripeptide derivatives, PY*L and AY*L (where Y* represents phosphotyrosine), which inhibit Stat3 biochemical activity and biological function. Here, we report novel peptidomimetic compounds based on PY*L (or AY*L) with substitution of the Y-1 residue by benzyl, pyridyl, or pyrazinyl derivatives that are selective and greater than 5-fold more potent in disrupting Stat3 activity in vitro than lead tripeptides. The biological activities of these derivatives mirror that originally observed for peptides. In this context, the representative peptidomimetic ISS 610 with 4-cyanobenzoate substitution inhibits constitutive Stat3 activity in Src-transformed mouse fibroblasts and human breast and lung carcinoma cells. This effect is not evident with the non-phosphorylated counterpart, ISS 610NP, consistent with interaction of peptidomimetics with the SH2 domain of Stat3. Moreover, ISS 610 induces cell growth inhibition and apoptosis of Src-transformed fibroblasts that contain persistently active Stat3. We present the first report of a peptidomimetic approach to design of small-molecule inhibitors of Stat3 that are also among the first examples of disruptors of transcription factor dimerization with the potential for novel cancer therapy.

Metabolic and electrolyte disturbance after cardiac arrest: How to deal with it.

Cardiac arrest (CA) is a sudden, severe event that causes a cascade of metabolic and electrolyte disturbances throughout the body triggered by a loss of cardiac output. Metabolic disturbances are primarily in the form of mixed metabolic and respiratory acidosis; dysglycaemia; and states of deficiency or excess in potassium, calcium, magnesium and lactate. It is known that persistent metabolic disturbances are associated with poor patient outcome following resuscitation from CA, but this might simply be a reflection of the severity of illness. Moreover, contemporary evidence for the management of metabolic disturbances to improve outcomes in these patients is scarce. Moreover, metabolic disturbances during the early post-resuscitation period remain poorly understood in terms of severity, duration and the influence of their post-resuscitation care and treatment on outcome. Although sufficient data suggest that extreme metabolic disturbances such as hypoglycaemia, severe hyperglycaemia, severe hypokalaemia and hyperkalaemia and hypomagnesaemia likely have a devastating effect and should be avoided, randomised controlled trial evidence is clearly need for the management of metabolic and electrolyte derangements in resuscitated CA patients.

Antiproliferative and phenotype-transforming antitumor agents derived from cysteine.

Selective destruction of malignant tumor cells without damaging normal cells is an important goal for cancer chemotherapy in the 21st century. Differentiating agents that transform cancer cells to either a nonproliferating or normal phenotype could potentially be tissue-specific and avoid side effects of current drugs. However, most compounds that are presently known to differentiate cancer cells are histone deacetylase inhibitors that are of low potency or suffer from low bioavailability, rapid metabolism, reversible differentiation, and nonselectivity for cancer cells over normal cells. Here we describe 36 nonpeptidic compounds derived from a simple cysteine scaffold, fused at the C-terminus to benzylamine, at the N-terminus to a small library of carboxylic acids, and at the S-terminus to 4-butanoyl hydroxamate. Six compounds were cytotoxic at nanomolar concentrations against a particularly aggressive human melanoma cell line (MM96L), four compounds showed selectivities of > or =5:1 for human melanoma over normal human cells (NFF), and four of the most potent compounds were further tested and found to be cytotoxic for six other human cancer cell lines (melanomas SK-MEL-28, DO4; prostate DU145; breast MCF-7; ovarian JAM, CI80-13S). The most active compounds typically caused hyperacetylation of histones, induced p21 expression, and reverted phenotype of surviving tumor cells to a normal morphology. Only one compound was given orally at 5 mg/kg to healthy rats to look for bioavailability, and it showed reasonably high levels in plasma (C(max) 6 microg/mL, T(max) 15 min) for at least 4 h. Results are sufficiently promising to support further work on refining this and related classes of compounds to an orally active, more tumor-selective, antitumor drug.

Beta-strand mimicking macrocyclic amino acids: templates for protease inhibitors with antiviral activity.

New amino acids are reported in which component macrocycles are constrained to mimic tripeptides locked in a beta-strand conformation. The novel amino acids involve macrocycles functionalized with both an N- and a C-terminus enabling addition of appendages at either end to modify receptor affinity, selectivity, or membrane permeability. We show that the cycles herein are effective templates within inhibitors of HIV-1 protease. Eleven compounds originating from such bifunctionalized cyclic templates are potent inhibitors of HIV-1 protease (Ki 0.3-50 nM; pH 6.5, I = 0.1 M). Unlike normal peptides comprising amino acids, five of these macrocycle-containing compounds are potent antiviral agents with sub-micromolar potencies (IC(50) 170-900 nM) against HIV-1 replication in human MT2 cells. The most active antiviral agents are the most lipophilic, with calculated values of LogD(6.5) > or = 4. All molecules have a conformationally constrained 17-membered macrocyclic ring that has been shown to structurally mimic a tripeptide segment (Xaa)-(Val/Ile)-(Phe/Tyr) of a peptide substrate in the extended conformation. The presence of two trans amide bonds and a para-substituted aromatic ring prevents intramolecular hydrogen bonds and fixes the macrocycle in the extended conformation. Similarly constrained macrocycles may be useful templates for the creation of inhibitors for the many other proteins and proteases that recognize peptide beta-strands.

Regioselective synthesis of antiparallel loops on a macrocyclic scaffold constrained by oxazoles and thiazoles.

The regioselective syntheses and structures are reported for two tris-macrocylic compounds, each possessing two antiparallel loops on a macrocyclic scaffold constrained by two oxazoles and two thiazoles. NMR solution structures show the loops projecting from the same face of the macrocycle. Such molecules are shown to be prototypes for mimicking multiple loops of proteins.[structure: see text]