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Background
We recently reported that palmitic acid (PA) is a novel and efficient CD4 fusion inhibitor to HIV-1 entry and infection. In the present report, based on in silico modeling of the novel CD4 pocket that binds PA, we describe discovery of highly potent PA analogs with increased CD4 receptor binding affinities (Kd) and gp120-to-CD4 inhibition constants (Ki). The PA analogs were selected to satisfy Lipinski''s rule of drug-likeness, increased solubility, and to avoid potential cytotoxicity.Principal Findings
PA analog 2-bromopalmitate (2-BP) was most efficacious with Kd ∼74 nM and Ki ∼122 nM, ascorbyl palmitate (6-AP) exhibited slightly higher Kd ∼140 nM and Ki ∼354 nM, and sucrose palmitate (SP) was least efficacious binding to CD4 with Kd ∼364 nM and inhibiting gp120-to-CD4 binding with Ki ∼1486 nM. Importantly, PA and its analogs specifically bound to the CD4 receptor with the one to one stoichiometry.Significance
Considering observed differences between Ki and Kd values indicates clear and rational direction for improving inhibition efficacy to HIV-1 entry and infection. Taken together this report introduces a novel class of natural small molecules fusion inhibitors with nanomolar efficacy of CD4 receptor binding and inhibition of HIV-1 entry. 相似文献754.
In several papers Arquès and Michel studied the maximal circular codes consisting of words of length 3 (or trinucleotides) on the genetic alphabet {A, C, G, T}. We present here some additional information on these codes. In particular, we study the growth function of the self-complementary circular codes and we prove that among them exactly 528 are maximal. 相似文献
755.
Mario Penna & Maricel Quispe 《Ethology : formerly Zeitschrift fur Tierpsychologie》2007,113(4):313-323
Localization of a sound source is important for animals in mating contexts: females generally orient towards signalling males, and males can estimate the position and quality of potential rivals. In anurans, the effect of sound direction on evoked vocal responses has been studied in males of Rana catesbeiana, which alter their vocal responses depending on the location of the stimulus. The current study explored the effects of sound direction in Eupsophus calcaratus, a frog that calls from inside burrows having resonance that would hinder the localization of incoming sounds. The vocal responses of 11 males to synthetic imitations of the conspecific advertisement call broadcast from loudspeakers positioned in front, to the right and left from the burrow openings were similar in terms of call rate, duration and latency. The invariance of the vocal responses indicates that for burrowing male frogs engaged in chorusing behaviour, the specific location of an opponent does not alter the persistence of vocal activity. 相似文献
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Mario Parisi Ricardo A. Dorr Marcelo Ozu Roxana Toriano 《Journal of biological physics》2007,33(5-6):331-343
This review focuses on studies of water movement across biological membranes performed over the last 50 years. Different scientific approaches had tried to elucidate such intriguing mechanism, from hypotheses emphasizing the role of the lipid bilayer to the cloning of aquaporins, the ubiquitous proteins described as specific water channels. Pioneering and clarifying biophysical work are reviewed beside results obtained with the help of recent sophisticated techniques, to conclude that great advances in the subject live together with old questions without definitive answers. 相似文献
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Gomes NC Borges LR Paranhos R Pinto FN Krögerrecklenfort E Mendonça-Hagler LC Smalla K 《Applied and environmental microbiology》2007,73(22):7392-7399
Polycyclic aromatic hydrocarbon (PAH) pollutants originating from oil spills and wood and fuel combustion are pollutants which are among the major threats to mangrove ecosystems. In this study, the composition and relative abundance in the sediment bacterial communities of naphthalene dioxygenase (ndo) genes which are important for bacterial adaptation to environmental PAH contamination were investigated. Three urban mangrove sites which had characteristic compositions and levels of PAH compounds in the sediments were selected. The diversity and relative abundance of ndo genes in total community DNA were assessed by a newly developed ndo denaturing gradient gel electrophoresis (DGGE) approach and by PCR amplification with primers targeting ndo genes with subsequent Southern blot hybridization analyses. Bacterial populations inhabiting sediments of urban mangroves under the impact of different sources of PAH contamination harbor distinct ndo genotypes. Sequencing of cloned ndo amplicons comigrating with dominant DGGE bands revealed new ndo genotypes. PCR-Southern blot analysis and ndo DGGE showed that the frequently studied nah and phn genotypes were not detected as dominant ndo types in the mangrove sediments. However, ndo genotypes related to nagAc-like genes were detected, but only in oil-contaminated mangrove sediments. The long-term impact of PAH contamination, together with the specific environmental conditions at each site, may have affected the abundance and diversity of ndo genes in sediments of urban mangroves. 相似文献