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At least 721 records · Page 40Linked to original sources
PubMed2001

The annual cycle of primary productivity in a tropical estuary: the inner regions of the Golfo de Nicoya, Costa Rica.

A one year cycle of primary productivity (PP) was studied using the "light and dark bottle" technique in the Golfo de Nicoya, located at 10 degrees N and 85 degrees W at the Pacific coast of Costa Rica. Samples were always incubated at 0, 1, 2, 3 and 4 m depth for 5 hrs from 8:30 till 13:30. The measurements were performed twice per month, first around high tide and one week later at low tide to account for tidal influences. This routine study was supplemented by special measurements about regional and short-term variations of primary productivity using the 14C-method, which mainly served to account for the shortcomings of the routinely employed incubation technique. The upper Golfo de Nicoya is an extremely productive, phytoplankton dominated estuarine system with an annual gross PP of 1037, a net PP of 610 and a community respiration of 427 g C m(-2) a(-1). Highest monthly PP values occurred during the dry season and at the beginning of the rainy season. Peaks in primary productivity coincided with massive blooms of red tide forming algae. Internal biological dynamics, estuarine circulation and land run-off are the most important nutrient sources. High water turbidity reduces the euphotic layer to 4-5 m depth, making the underwater light regime the rate limiting factor. On an annual basis, 41% of the organic carbon produced in the system is already consumed in the euphotic layer. Considering the entire water column (mean depth at mean tidal water level is around 7.7 m) 79% is consumed in the pelagial. Taking into account the organic material consumed and stored in the sediments the carbon budget of the upper gulf is probably balanced. Since, however, the system receives a considerable amount of organic material from its terrestrial surroundings (especially from the mangrove forests), a surplus of organic carbon is exported from the upper Golfo de Nicoya, which enhances the overall water productivity of the lower gulf and the adjacent area.

Journal Article↗
PubMed2004

[Effects of environmental factors on catch variation of main species of stow net fisheries in East China Sea].

Stow net fishery is one of the important fishing methods in the East China Sea. This paper used the generalized additive models (GAMs) to quantitatively describe the relationships between stow net catch and environmental factors (sea surface temperature SST, water depth, fishing position and tide) in the East China Sea. The results indicated that each factor had its own nonlinear effect on the catch per unit effort (CPUE) of haitail (Trichiurus japonicus), small yellow croaker (Larimichthys polyactis) and butter fish (Pampus spp.), and SST and water depth were the key factors. The GAMs' fitting results showed that SST had the strongest effect on the catch per unit effort of haitail, and water depth had the second one. The effects of fishing location and tide were very small. Water depth was the most influential variable when adjusted for the effects on small yellow croaker. SST, fishing location and tide had similar effects. Meanwhile, water depth and SST were the key factors affecting the catch per unit effort of butter fish. They had similar intensity.

China↗
PubMed1990

Specificities of autoinhibitory domain peptides for four protein kinases. Implications for intact cell studies of protein kinase function.

Synthetic peptides corresponding to the autoinhibitory domains of calcium/calmodulin-dependent protein kinase II (CaMK-(281-309)), smooth muscle myosin light chain kinase (MLCK-(480-501)), and protein kinase C (PKC-(19-36)) as well as a peptide derived from the heat-stable inhibitor of cAMP-dependent protein kinase (PKI-tide) were tested for their inhibitory specificities. The inhibitory potencies of the four peptides were determined for each of the four protein kinases using both peptide substrates (at approximate Km concentrations) and protein substrates (at concentrations less than Km). In agreement with previous studies PKI-tide was a specific and potent inhibitor of only cAMP kinase, and none of the other inhibitory peptides gave significant inhibition of cAMP kinase at concentrations of less than 100 microM. With synthetic peptide substrates, PKC-(19-36) strongly inhibited native PKC (IC50 less than 1 microM) but also significantly inhibited autophosphorylated CaMK-II (IC50 = 30 microM) and proteolytically activated MLCK (IC50 = 35 microM). MLCK-(480-501) potently inhibited MLCK (IC50 = 0.25 microM) and also strongly inhibited both PKC and CaMK-II (IC50 = 1.4 and 1.7 microM, respectively). CaMK-(281-309) inhibited autophosphorylated CaMK-II, PKC, and proteolyzed MLCK almost equally (IC50 = 10, 38, and 48 microM, respectively). Qualitatively similar results were obtained with protein substrates. These studies validate the use of PKI-tide as a specific inhibitor of cAMP kinase in intact cell studies and suggest that PKC-(19-36) can also be used but only within a narrow concentration range. However, the autoinhibitory domain peptides from MLCK and CaMK-II are not sufficiently specific to be used in similar investigations.

Amino Acid Sequence↗
PubMed1993

Control of Aedes dorsalis with sustained-release methoprene pellets in a saltwater marsh.

The efficacy and persistence of sustained-release methoprene (Altosid) pellets were evaluated in a tidal, saltwater marsh primarily against Aedes dorsalis. Pellets were applied prior to marsh inundation at 3.4 kg/ha. They provided > 99% control through the July and August high tide series (up to 42 days posttreatment), 86.4% control during the November high tide series (131 days posttreatment) and 66.6% control during the February high tide series (240 days posttreatment). Proportions of partially emerged adults increased over the course of the study, constituting 0, 0.7, 16.2 and 18.9% of the unsuccessfully emerging mosquitoes in July, August, November and February, respectively. Sixty-six percent of the completely emerged mosquitoes from the treated region of the marsh were found dead on the water surface, compared with only 0.7% from the control region. This implies that exposure to low concentrations of methoprene impairs the ability of the completely emergent mosquito to fly.

Aedes↗
PubMed1993

Application of radar rainfall estimates for surveillance of Aedes taeniorhynchus larvae.

A preliminary investigation of land-based radar rainfall estimates for surveillance of Aedes taeniorhynchus larvae was conducted from January 1 to May 21, 1991 in Collier County, FL. Rainfall estimates from the National Weather Service RADAP II radar system, supplemented with tide gauge data, served as criteria for larval inspection. Rain, rain+tide and tide, respectively, triggered 48, 26 and 26% of the 14 proposed inspection trips. This system detected 7/8 larval broods found by Collier Mosquito Control District surveillance; the only brood not detected consisted of stragglers from an earlier brood exposed to cool weather and methoprene. A QUICKBASIC program that extracts Cartesian coordinates and rainfall estimates from RADAP II B-SCAN data was developed.

Aedes↗
PubMed1990

Urine acid output as a test of completeness of vagotomy.

Peak acid output in response to sham feeding and changes in urine acid output 2 and 3 hours after a test meal have been measured in 20 normal volunteers, 17 asymptomatic patients after vagotomy, six patients with recurrent duodenal ulcer after vagotomy and ten normal subjects given a 48-h course of ranitidine, 150 mg 12-hourly. Gastric peak acid output in normal volunteers ranged from 6.9 to 22.1 mmol/h. All asymptomatic patients after vagotomy had a peak acid output less than 7 mmol/h, consistent with complete vagotomy. Five patients with recurrent ulcer had a peak acid output greater than 8 mmol/h, suggesting an incomplete vagotomy. Urine acid output after a test meal, expressed as the change from the basal rate of acid output, was always in a negative direction in normal subjects (fall in acid output = postprandial alkaline tide). This change was abolished in patients with complete vagotomy, in whom urine acid output increased after a meal. In five patients with incomplete vagotomy (and one other with recurrent ulcer and unknown vagal status) the urine acid output changed in a negative direction after a test meal. The relationship of urine acid output to gastric secretion was confirmed by the abolition of the postprandial alkaline tide in normal subjects given ranitidine. The results in patients with incomplete vagotomy did not overlap with those from patients with complete vagotomy. This suggests that this test could be used for the routine postoperative assessment of completeness of vagotomy.

Adolescent↗
PubMed2006

Fluorescent N2,N3-epsilon-adenine nucleoside and nucleotide probes: synthesis, spectroscopic properties, and biochemical evaluation.

N1,N(6)-ethenoadenine, epsilon-A, nucleos(t)ides have been previously applied as fluorescent probes in numerous biochemical systems. However, these epsilon-A analogues lack the H-bonding capability of adenine. To improve the fluorescence characteristics while preserving the H-bonding pattern required for molecular recognition, we designed a novel probe: N(2),N3-etheno-adenosine, (N(2),N3-epsilon-A). Here, we describe four novel syntheses of the target epsilon-nucleoside and related analogues. These methods are short, facile, and provide the product regiospecifically. In addition, we report the absorption and emission spectra of N(2),N3-epsilon-A and the dependence of the spectral features on the pH and polarity of the medium. Specifically, maximum emission of N(2),N3-epsilon-A in water is observed at 420 nm (phi=0.03, excitation at 290 nm). The biochemical relevance of the new probe was evaluated with respect to the P2Y(1) receptor and NTPDases 1 and 2. N(2),N3-epsilon-ATP was found to be almost equipotent with ATP at the P2Y(1) receptor and was hydrolyzed by NTPDases 1 and 2 at about 80 % of the rate of ATP. Furthermore, protein binding does not seem to shift the fluorescence of N(2),N3-epsilon-ATP. Based on the fluorescence and full recognition by ATP-binding proteins, we propose N(2),N3-epsilon-ATP and related nucleo(s)tides as unique probes for the investigation of adenine nucleo(s)tide-binding proteins as well as for other biochemical applications.

Adenine↗
PubMed2026

Multi-Omics Integration Identifies a Five-Gene Metabolic Signature With Experimental Validation in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is hallmarked by profound metabolic reprogramming; however, its intricate crosstalk with the tumor immune microenvironment (TIME) and its clinical ramifications remain inadequately elucidated. This study aims to systematically decipher the metabolic-immune interplay in ccRCC through multi-omics integration, with the goal of identifying robust prognostic biomarkers and actionable therapeutic vulnerabilities. AIMS: This study aims to systematically decipher the metabolic-immune interplay in clear cell renal cell carcinoma (ccRCC) through multi‑omics integration, and to identify robust prognostic biomarkers and actionable therapeutic vulnerabilities that can inform precision risk stratification and individualized treatment strategies. METHODS: We integrated bulk transcriptomic, genomic, and clinical data from multiple ccRCC cohorts. Differential expression and functional enrichment analyses were performed to characterize metabolic pathway alterations. Mendelian randomization (MR) was employed to infer causal relationships between metabolic disorders and ccRCC risk. A machine learning-based prognostic framework, incorporating SHAP (SHapley Additive exPlanations) for feature interpretability, was constructed and rigorously validated. TIME heterogeneity was dissected using deconvolution algorithms, while drug sensitivity, tumor mutation burden (TMB), and TIDE scores were utilized to assess therapeutic responses and immune evasion. Candidate gene function was evaluated through in vitro gain- and loss-of-function assays, with expression validated via TCGA, HPA, western blot, and qRT-PCR. RESULTS: Enrichment analysis identified coordinated dysregulation in lipid metabolism, energy homeostasis, and hypoxia response pathways. MR analysis confirmed lipid metabolism disorders as a causal risk factor for ccRCC. Our machine-learning model, centered on five core SHAP-identified features (SUCLA2, ACAT1, PC, SUCLG1, and HMGCS2), demonstrated superior predictive accuracy over conventional clinical staging. Immune profiling unveiled dichotomous TIME states: the low-risk group retained active immune surveillance, whereas the high-risk group was enriched with immunosuppressive subsets. Drug sensitivity screening pinpointed LY2109761 and carmustine as high-risk-specific candidate agents. Furthermore, TMB and TIDE analyses stratified high-risk patients displaying genomic instability and immune evasion phenotypes. Functionally, SUCLA2 knockdown significantly enhanced ccRCC cell proliferation and invasion, while its overexpression suppressed these malignant phenotypes, corroborating its tumor-suppressive role. Expression patterns of the hub genes were consistently validated across multi-level datasets and experimental assays. CONCLUSION: This study establishes a precision oncology framework for ccRCC by functionally linking metabolic biomarkers, immunophenotypes, and stratified therapeutic strategies. Importantly, we identify SUCLA2 as a potential functional tumor suppressor and a promising target for further mechanistic and translational investigation.

Humans↗
PubMed2002

Optimization of signal behavior in the transition to driven equilibrium in steady-state free precession sequences.

A new technique to avoid the initial signal fluctuations in steady-state free precession (SSFP)-sequences, such as trueFISP, FIESTA, and refocused FFE, is presented. The "transition into driven equilibrium" (TIDE) sequence uses modified flip angles over the initialization phase of a SSFP experiment, which not only avoids image artifacts but also improves the signal-to-noise ratio (SNR) and contrast behavior compared to conventional approaches. TIDE is demonstrated to be robust against variations of T(1) and T(2), and leads to a monotonous signal evolution for off-resonance spins. The basic principles can also be applied repetitively to optimize continuous 3D acquisitions.

Head↗
PubMed1999

Endogenous rhythms of locomotor activity in the high-shore limpet, Helcion pectunculus (Patellogastropoda).

Helcion pectunculus, a high-shore, crevice-dwelling limpet, is active during nocturnal low tides and during daytime low tides whilst in the shade. We examined whether this activity is controlled by an internal clock or purely by exogenous stimuli, such as light levels and tidal phase. Maximum entropy spectral analysis (MESA) revealed that the limpets possess a free-running endogenous rhythm of locomotor activity with both circadian (period 28.1 h) and circatidal (period 13.8 h) components. We suggest that this rhythm plays a role in allowing individuals to avoid unfavourable environmental conditions. The exogenous entrainment factor of the endogenous circatidal rhythm in H. pectunculus is the time of exposure to air, whilst the zeitgeber for the circadian component is not yet known. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Geographical variation in temporal and spatial vocalization patterns of male harbour seals in the mating season.

In the aquatically mating harbour seal, Phoca vitulina, oestrous females show marked differences in spatial and temporal distribution between geographical areas. This suggests that the males' display behaviour may also vary between areas. We recorded male vocalizations in two areas, the Moray Firth and Orkney, U.K. In the Moray Firth, females haul out on a few intertidal sandbars and travel along predictable routes to forage at sea. In Orkney, female haul out sites are much less influenced by tidal availability and females are much more dispersed. In the Moray Firth, males vocalized only during a short mating season, from 1 July to 12 August. Vocalizations varied significantly with the tide, the peak at high tide clearly coinciding with the period when most females were in the water. In contrast, vocalizations in Orkney were significantly related to both tidal and diel patterns. We suggest that the timing of male vocalizations reflects differences in female availability between sites. In the inner Moray Firth, vocalizations were heard throughout the females' range, whereas vocalizations in Orkney were heard only in two discrete areas. However, at both sites the density of vocalizing males was highest in narrow channels and/or along predictable female travel routes. Therefore, males clearly adapt their temporal and spatial behaviour patterns to variations in female distribution and density. These results suggest that male mating strategies in aquatically mating pinnipeds are more variable than was previously envisaged. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2001

Biotransformation, endocrine, and genetic responses of Anguilla anguilla L. to petroleum distillate products and environmentally contaminated waters.

The European eel (Anguilla anguilla L.) was exposed to diesel oil water-soluble fraction (DWSF) and gasoline water-soluble fraction (GWSF). The potential of these fractions to induce endocrine disruption, carbohydrate, and xenobiotic metabolism effects, as well as genotoxic responses, was investigated in a time-course laboratory study (3 h to 6 days). Both water-soluble fractions induced a time-related increase in liver ethoxyresorufin-O-deethylase (EROD) activity, as well as the appearance of erythrocytic nuclear abnormalities (ENA) after a 6-day exposure, revealing its genotoxic properties. Initially, DWSF exposure revealed an inhibition of the typical stress responses demonstrated by plasma cortisol and lactate decrease. Nevertheless, this effect progressively disappeared, allowing a plasma glucose and lactate increase after 6 days of exposure. Fish exposed to GWSF exhibited a liver alanine transaminase (ALT) activity increase after a short exposure while the longest exposure revealed liver damage expressed as an ALT activity decrease. A field caging experiment, carried out in a harbor area (Aveiro Lagoon, Portugal), and a complementary laboratory experiment were designed to assess the influence of the daily tide dynamic on polyaromatic hydrocarbon water distribution and effects on liver EROD and ALT activities, as well as ENA frequency. Eels exposed to low- and high-tide harbor waters, in the laboratory, exhibited a similar degree of genotoxicity, whereas clear differences were observed as EROD induction. In the field experiment, caged eels did not display significant responses enhancing the relevance of natural environmental factors on toxicity mechanisms as well as on the apparent lack of toxicity in harbor waters.

Anguilla↗
PubMed2001

Factors Influencing Bacterial Production in a Shallow Estuarine System.

The bacterioplankton of the marine and brackish water zones of the complex system Ria de Aveiro was characterized as profiles of bacterial abundance and biomass productivity. During the warm season, total bacteria ranged from 0.2 to 8.5 x 109 cells L-1 and active bacteria number from 0.1 to 3.1 x 109 cells L-1. Total and active bacterial numbers were, on average, three times higher in brackish than in marine water. Bacterial productivity on different dates and different tides in the marine zone varied from 0.05 to 4.5 mg C L-1 h-1. Here the average productivity (1.1 mg C L-1 h-1) was 3.5 times less than in brackish water (average 3.8 mg C L-1 h-1; range 0.7-14.2 mg C L-1 h-1). Specific productivity varied from 0.05 to 2.61 fg C cell-1 h-1, a range that was similar throughout the ecosystem. However, specific productivity per active cell was 19% higher in brackish water. Bacterial production variation was best explained by the number of active bacteria, which, in turn, was highly associated with total bacterial number, temperature, and particulate organic carbon. In the marine zone, bacterial production was also influenced by depth and salinity. In the brackish zone, the set of independent variables explained a smaller percentage of bacterial production variation than in marine zone, suggesting greater importance of other variables. In the marine zone, and mainly near low tide, productivity was significantly higher (average 3.3 times) at the surface (down to 0.5 m) than in the deeper layers of the water column. This stratification of bacterial productivity was linked to the increased specific productivity per active cell, as no modification in the proportion of active cells in the population could be detected. The vertical profile of bacterial production in the deeper zone of this estuarine ecosystem, in which no clear salinity or thermal stratification occurs throughout the tidal cycle, seemed to reflect a biochemical stratification generated by increased phytoplankton exudation and/or by photochemical transformation of semilabile or recalcitrant organic compounds. Shallower water masses tend to blur this surface effect. The relative importance of photochemical transformation in the pattern of estuarine bacterial production will therefore tend to vary with the bathymetry of the system.

Journal Article↗
PubMed2004

Circatidal variation in epithelial cell proliferation in the mussel digestive gland and stomach.

Epithelial cell renewal in mussel ( Mytilus galloprovincialis, Lmk) digestive gland and stomach was investigated by bromodeoxyuridine (BrdU) immunohistochemistry. Mussels were exposed to 4 mg BrdU/l seawater continuously. Starting at 6 h after treatment, samples were collected every 2 h for 2 days and BrdU labelling was estimated by direct counting at the light microscope, with values being noted per thousand BrdU-positive cells. BrdU-positive reaction was observed in the nuclei of digestive, basophilic, duct and stomach cells, and in haemocytes. Cell renewal in digestive diverticula was synchronised following a circatidal pattern: BrdU labelling increased during low tide and decreased during high tide. Clearcut mitotic figures were identified in digestive cells, thereby confirming that mature cell types proliferate, in agreement with results from immunohistochemistry for proliferating cell nuclear antigen and BrdU. Epithelial cell renewal in the stomach also appeared to be synchronised.

Animals↗
PubMed2004

Competitive interactions in macroinfaunal animals of exposed sandy beaches.

The influence of biotic interactions in structuring macroinfaunal communities of exposed sandy beaches, an unstable habitat characterized by strong physical forces, is generally considered negligible. We investigated the hypothesis that competitive interactions during burrowing could potentially affect the intertidal distribution and abundance of macroinfaunal animals of sandy beaches using two species of invertebrates, a hippid crab, Emerita analoga, and a bivalve, Mesodesma donacium, common along the coast of Chile. Spatial overlap in the intertidal distributions of these species was dynamic, varying with abundance, location, time of year and tide. Highest density zones of each species were often distinctly separated at low tide and spatial overlap in their distributions decreased significantly with increasing density, suggesting density dependence of the interactions. Negative relationships between densities of the two species at the smallest spatial scale examined also suggested active interactions among individuals. Over a tidal cycle, peak densities of the two species overlapped suggesting that interactions could occur frequently. Burrowing performance of E. analoga varied between size classes in three experimental densities of clams (5, 10 and 15 clams 0.008 m(-2)) and in controls with no clams. Burrowing times of large crabs were significantly longer (approximately twofold) in all densities of clams than in controls, while those of small crabs did not differ significantly among treatments and controls. Large crabs also displaced clams from the sand while burrowing suggesting that two mechanisms of direct interference can occur, both of which could increase exposure of individuals involved to active swash and transport across or along the beach with potentially negative consequences. Our results suggest that competitive interactions capable of affecting zonation and population and community biology on a number of scales can occur among burrowing macroinfauna on exposed sandy beaches. Those interactions could be more ecologically significant than previously appreciated and may contribute to patterns observed in community structure and zonation on sandy beaches. Our results illustrate the potential importance of negative biological interactions in a physically stressful environment.

Analysis of Variance↗
PubMed2006

Changes of hydrological environment and their influences on coastal wetlands in the southern Laizhou Bay, China.

The structure and function of the coastal wetland ecosystem in the southern Laizhou Bay have been changed greatly and influenced by regional hydrological changes. The coastal wetlands have degraded significantly during the latest 30 years due to successive drought, decreasing of runoff, pollution, underground saline water intrusion, and aggravating marine disasters such as storm tides and sea level rising. Most archaic lakes have vanished, while artificial wetlands have been extending since natural coastal wetlands replaced by salt areas and ponds of shrimps and crabs. The pollution of sediments in inter-tidal wetlands and the pollution of water quality in sub-tidal wetlands are getting worse and therefore "red tides" happen more often than before. The biodiversity in the study area has been decreased. Further studies are still needed to protect the degraded coastal wetlands in the area.

Biodiversity↗
PubMed2005

Arterial acid-base status during digestion and following vascular infusion of NaHCO(3) and HCl in the South American rattlesnake, Crotalus durissus.

Digestion is associated with gastric secretion that leads to an alkalinisation of the blood, termed the "alkaline tide". Numerous studies on different reptiles and amphibians show that while plasma bicarbonate concentration ([HCO(3)(-)](pl)) increases substantially during digestion, arterial pH (pHa) remains virtually unchanged, due to a concurrent rise in arterial PCO(2) (PaCO(2)) caused by a relative hypoventilation. This has led to the suggestion that postprandial amphibians and reptiles regulate pHa rather than PaCO(2). Here we characterize blood gases in the South American rattlesnake (Crotalus durissus) during digestion and following systemic infusions of NaHCO(3) and HCl in fasting animals to induce a metabolic alkalosis or acidosis in fasting animals. The magnitude of these acid-base disturbances were similar in magnitude to that mediated by digestion and exercise. Plasma [HCO(3)(-)] increased from 18.4+/-1.5 to 23.7+/-1.0 mmol L(-1) during digestion and was accompanied by a respiratory compensation where PaCO(2) increased from 13.0+/-0.7 to 19.1+/-1.4 mm Hg at 24 h. As a result, pHa decreased slightly, but were significantly below fasting levels 36 h into digestion. Infusion of NaHCO(3) (7 mmol kg(-1)) resulted in a 10 mmol L(-1) increase in plasma [HCO(3)(-)] within 1 h and was accompanied by a rapid elevation of pHa (from 7.58+/-0.01 to 7.78+/-0.02). PaCO(2), however, did not change following HCO(3)(-) infusion, which indicates a lack of respiratory compensation. Following infusion of HCl (4 mmol kg(-1)), plasma pHa decreased by 0.07 units and [HCO(3)(-)](pl) was reduced by 4.6 mmol L(-1) within the first 3 h. PaCO(2), however, was not affected and there was no evidence for respiratory compensation. Our data show that digesting rattlesnakes exhibit respiratory compensations to the alkaline tide, whereas artificially induced metabolic acid-base disturbances of same magnitude remain uncompensated. It seems difficult to envision that the central and peripheral chemoreceptors would experience different stimuli during these conditions. One explanation for the different ventilatory responses could be that digestion induces a more relaxed state with low responsiveness to ventilatory stimuli.

Acidosis↗
PubMed2006

Beta strand peptidomimetics as potent PDZ domain ligands.

The search for general strategies for inhibiting protein-protein interactions has been stimulated by recognition of the key role they play in virtually every process of living systems. Multiprotein complex assembly and localization by PDZ domain-containing proteins exemplify processes critical to cell physiology and function that are mediated by beta strand association. Here we describe the development of substituted "@-tides," protease-resistant peptidomimetics incorporating conformationally restricted amino acid surrogates that reproduce the hydrogen-bonding pattern and side-chain functionality of a beta strand. The synthetic flexibility and generality of the substituted @-tide design was demonstrated by the synthesis of a panel of ligands for the alpha1-syntrophin PDZ domain. The rational design of a small molecule of unprecedented affinity for the PDZ domain suggests that these peptidomimetics may provide a general method for inhibiting protein-protein interactions involving extended peptide chains.

Biomimetics↗