What are the checkpoints during cell cycle?3 answersCell cycle checkpoints are regulatory mechanisms that ensure the proper progression of the cell cycle and maintain genomic integrity. These checkpoints monitor various events, including cell size, DNA replication, chromosome integrity, and accurate chromosome segregation during mitosis. Recent studies have revealed the existence of more subtle and sophisticated checkpoint regulation mechanisms that allow cells to adapt their cell cycle program to changing conditions, such as replication impediments and endogenous replication stress. In addition to checkpoints for DNA replication and segregation, there are also checkpoints that ensure the division of cytoplasmic components, such as organelles, is properly regulated. The activation and inactivation of kinases and phosphatases play a crucial role in checkpoint regulation, with the interphase kinase Wee1 and the mitotic phosphatase Cdc25 controlling cyclin-dependent kinases (CDKs) in an opposite manner to establish a stable G2 phase and add checkpoints to the cell cycle.
How can in vitro anti mitotic activity in psoriasis be checked?5 answersIn vitro anti-mitotic activity in psoriasis can be checked using various methods. One approach is to use high-throughput screening (HTS) of large compound libraries using keratinocyte proliferation models. The radioactive [3H]-thymidine incorporation assay is considered the gold standard for evaluating keratinocyte proliferation in vitro. However, there are also several simple and reliable colorimetric and fluorimetric methods available, such as MTT, NRU, SRB, CVS, CAM, and AB assays, which can be used to measure keratinocyte proliferation in 96-well formats. These methods can be used to determine the concentrations that induce 50% growth inhibition (GI50) for potential anti-psoriatic agents. Additionally, in vitro labelling with tritiated thymidine can be used to investigate the mitotic activity of uninvolved skin and buccal mucosa in patients with active psoriasis.
What are the most promising research directions in the field of polyketides?4 answersRecent research highlights in the field of polyketides have focused on the synthesis of natural products and structural analogs as potential anticancer agents. The halichondrins, eribulin, bryostatin, dictyostatin, spongistatin, peloruside, spirastrellolide, palmerolide, reidispongiolide, spirangien, and saliniketals have all shown promise in anticancer drug discovery. Efficient total synthesis plays a crucial role in providing a sustainable supply of these compounds for drug development.Another research direction involves an iterative method for synthesizing polyketides using decarboxylative dehydration condensation with a malonic acid half thioester. This method allows for chain elongation and regeneration of the carboxylic acid functionality for subsequent elongation steps.Additionally, a platform has been developed for engineering polyketides in E. coli, enabling the creation of new compounds for research and modification of known polyketides to improve their pharmacological properties. This platform could potentially be used to produce low-toxicity doxorubicin analogs.
Is there a proof reading mechanism for polyketide synthases?5 answersPolyketide synthases (PKSs) have a proofreading mechanism to correct mistakes during biosynthesis. Acyltransferases play a role in error correction by hydrolyzing key biosynthetic intermediates. The turnstile mechanism synchronizes the action of the entire assembly line, preventing the acylation of the ketosynthase domain until the product of the prior catalytic cycle has been passed to the downstream module. This mechanism ensures directional biosynthesis and allows for the precise control of stereochemistry in PKSs. In trans-acyltransferase (trans-AT) modular PKSs, a docking domain (DD) at the C terminus of the ketosynthase interacts with the downstream dehydratase, facilitating communication between the two domains. This interaction is crucial for the correct assembly and functioning of the PKS complex.
What are polyketide's role for the host organism?3 answersPolyketides play important roles in their host organisms. They act as chemical triggers of sporulation and granulose accumulation in the anaerobic bacterium Clostridium acetobutylicum. In the red goldenrod aphid Uroleucon nigrotuberculatum, polyketide pigments inhibit the growth of pathogenic fungi, providing chemopreventive effects at the individual and species level. Naturally occurring polyketides and their derivatives have significant pharmaceutical value and are used in the production of drugs. The rough lemon pathotype of Alternaria alternata produces a polyketide toxin essential for its pathogenicity. In the fungus Hericium erinaceus, polyketide synthases are involved in the biosynthesis of orsellinic acid and its analogs, which have potential industrial applications.
What are the efffects of polyketides and PKSs in nature?4 answersPolyketides are biologically active and structurally diverse compounds found in nature. They are produced by polyketide synthases (PKSs) and have high biological activity. Polyketides have significant pharmaceutical value and are used in the production of drugs, pesticides, and biological probes. They are also employed by living organisms to provide survival advantages. Polyketides display a vast array of structural diversity, including linear, polycyclic, and macrocyclic forms. The biosynthesis of polyketides can be manipulated through the reprogramming of PKSs, and an understanding of gene cluster evolution provides insights for the production of unnatural polyketides. Modular PKSs are nature's platform for the expansion of chemical diversity, allowing for the introduction of unique chemical functionality into polyketide structures. Overall, polyketides and PKSs play important roles in nature, offering potential for the development of novel compounds with various applications.