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Protein Science : a Publication of the... Nov 1995The molar absorption coefficient, epsilon, of a protein is usually based on concentrations measured by dry weight, nitrogen, or amino acid analysis. The studies reported...
The molar absorption coefficient, epsilon, of a protein is usually based on concentrations measured by dry weight, nitrogen, or amino acid analysis. The studies reported here suggest that the Edelhoch method is the best method for measuring epsilon for a protein. (This method is described by Gill and von Hippel [1989, Anal Biochem 182:319-326] and is based on data from Edelhoch [1967, Biochemistry 6:1948-1954]). The absorbance of a protein at 280 nm depends on the content of Trp, Tyr, and cystine (disulfide bonds). The average epsilon values for these chromophores in a sample of 18 well-characterized proteins have been estimated, and the epsilon values in water, propanol, 6 M guanidine hydrochloride (GdnHCl), and 8 M urea have been measured. For Trp, the average epsilon values for the proteins are less than the epsilon values measured in any of the solvents. For Tyr, the average epsilon values for the proteins are intermediate between those measured in 6 M GdnHCl and those measured in propanol. Based on a sample of 116 measured epsilon values for 80 proteins, the epsilon at 280 nm of a folded protein in water, epsilon (280), can best be predicted with this equation: epsilon (280) (M-1 cm-1) = (#Trp)(5,500) + (#Tyr)(1,490) + (#cystine)(125) These epsilon (280) values are quite reliable for proteins containing Trp residues, and less reliable for proteins that do not. However, the Edelhoch method is convenient and accurate, and the best approach is to measure rather than predict epsilon.
Topics: 1-Propanol; Chemical Phenomena; Chemistry, Physical; Cystine; Guanidine; Guanidines; Proteins; Solvents; Spectrophotometry, Ultraviolet; Tryptophan; Tyrosine; Urea; Water
PubMed: 8563639
DOI: 10.1002/pro.5560041120 -
Bioorganic Chemistry Sep 2023Guanidines are fascinating small nitrogen-rich organic compounds, which have been frequently associated with a wide range of biological activities. This is mainly due to... (Review)
Review
Guanidines are fascinating small nitrogen-rich organic compounds, which have been frequently associated with a wide range of biological activities. This is mainly due to their interesting chemical features. For these reasons, for the past decades, researchers have been synthesizing and evaluating guanidine derivatives. In fact, there are currently on the market several guanidine-bearing drugs. Given the broad panoply of pharmacological activities displayed by guanidine compounds, in this review, we chose to focus on antitumor, antibacterial, antiviral, antifungal, and antiprotozoal activities presented by several natural and synthetic guanidine derivatives, which are undergoing preclinical and clinical studies from January 2010 to January 2023. Moreover, we also present guanidine-containing drugs currently in the market for the treatment of cancer and several infectious diseases. In the preclinical and clinical setting, most of the synthesized and natural guanidine derivatives are being evaluated as antitumor and antibacterial agents. Even though DNA is the most known target of this type of compounds, their cytotoxicity also involves several other different mechanisms, such as interference with bacterial cell membranes, reactive oxygen species (ROS) formation, mitochondrial-mediated apoptosis, mediated-Rac1 inhibition, among others. As for the compounds already used as pharmacological drugs, their main application is in the treatment of different types of cancer, such as breast, lung, prostate, and leukemia. Guanidine-containing drugs are also being used for the treatment of bacterial, antiprotozoal, antiviral infections and, recently, have been proposed for the treatment of COVID-19. To conclude, the guanidine group is a privileged scaffold in drug design. Its remarkable cytotoxic activities, especially in the field of oncology, still make it suitable for a deeper investigation to afford more efficient and target-specific drugs.
Topics: Male; Humans; Guanidine; COVID-19; Guanidines; Anti-Infective Agents; Antineoplastic Agents; Anti-Bacterial Agents; Neoplasms; Antihypertensive Agents; Antiviral Agents
PubMed: 37209561
DOI: 10.1016/j.bioorg.2023.106600 -
Marine Drugs Sep 2022A marine natural product possesses a diverse and unique scaffold that contributes to a vast array of bioactivities. Tricyclic guanidine alkaloids are a type of scaffold... (Review)
Review
A marine natural product possesses a diverse and unique scaffold that contributes to a vast array of bioactivities. Tricyclic guanidine alkaloids are a type of scaffold found only in marine natural products. These rare skeletons exhibit a wide range of biological applications, but their synthetic approaches are still limited. Various stereochemical assignments of the compounds remain unresolved. Batzelladine and ptilocaulins are an area of high interest in research on tricyclic guanidine alkaloids. In addition, mirabilins and netamines are among the other tricyclic guanidine alkaloids that contain the ptilocaulin skeleton. Due to the different structural configurations of batzelladine and ptilocaulin, these two main skeletons are afforded attention in many reports. These two main skeletons exhibit different kinds of compounds by varying their ester chain and sidechain. The synthetic approaches to tricyclic guanidine alkaloids, especially the batzelladine and ptilocaulin skeletons, are discussed. Moreover, this review compiles the first and latest research on the synthesis of these compounds and their bioactivities, dating from the 1980s to 2022.
Topics: Alkaloids; Biological Products; Esters; Guanidine; Guanidines; Stereoisomerism
PubMed: 36135769
DOI: 10.3390/md20090579 -
Molecules (Basel, Switzerland) Oct 2019Antimicrobial resistance has been seriously threatening human health, and discovering new antimicrobial agents from the natural resource is still an important pathway... (Review)
Review
Antimicrobial resistance has been seriously threatening human health, and discovering new antimicrobial agents from the natural resource is still an important pathway among various strategies to prevent resistance. Guanidine-containing polyhydroxyl macrolides, containing a polyhydroxyl lactone ring and a guanidyl side chain, can be produced by many actinomycetes and have been proved to possess many bioactivities, especially broad-spectrum antibacterial and antifungal activities. To explore the potential of these compounds to be developed into new antimicrobial agents, a review on their structural diversities, spectroscopic characterizations, bioactivities, acute toxicities, antimicrobial mechanisms, and the structure-activity relationship was first performed based on the summaries and analyses of related publications from 1959 to 2019. A total of 63 guanidine-containing polyhydroxyl macrolides were reported, including 46 prototype compounds isolated from 33 marine and terrestrial actinomycetes and 17 structural derivatives. Combining with their antimicrobial mechanisms, structure-activity relationship analyses indicated that the terminal guanidine group and lactone ring of these compounds are vital for their antibacterial and antifungal activities. Further, based on their bioactivities and toxicity analyses, the discovery of guanidyl side-chain targeting to lipoteichoic acid of indicated that these compounds have a great potency to be developed into antimicrobial and anti-inflammatory drugs.
Topics: Guanidine; Macrolides; Phylogeny; Spectrum Analysis; Structure-Activity Relationship; Toxicity Tests, Acute
PubMed: 31671653
DOI: 10.3390/molecules24213913 -
International Journal of Molecular... Dec 2022The cycloaddition of simple alkyl-substituted guanidine derivatives is an interesting approach toward polycyclic superbases and guanidine-based organocatalysts. Due to...
The cycloaddition of simple alkyl-substituted guanidine derivatives is an interesting approach toward polycyclic superbases and guanidine-based organocatalysts. Due to the high nucleophilicity of guanidines, an aza-Michael reaction with dienophiles is more common and presents a huge obstacle in achieving the desired synthetic goal. Our preliminary investigations indicated that the proton could act as a suitable protecting group to regulate the directionality of the reaction. To investigate the role of the protonation state and type of anion, the reactivity of furfuryl guanidines with dimethyl acetylenedicarboxylate was explored. Furfuryl guanidines showed a strong reaction dependence on the nucleophilicity of the counterion and the structure of guanidine. While the reaction of with the guanidinium halides provided products of an aza-Michael addition, Diels-Alder cycloaddition occurred if non-nucleophilic hexafluorophosphate salts were used. Depending on the structure and the reaction conditions, oxanorbornadiene products underwent subsequent intramolecular cyclization. A tendency toward intramolecular cyclization was interpreted in terms of the p of different positions of the guanidine functionality in oxanorbornadienes. New polycyclic guanidines had a slightly decreased p in acetonitrile and well-defined geometry suitable for the buildup of selective sensors.
Topics: Guanidine; Guanidines; Cyclization; Anions
PubMed: 36555678
DOI: 10.3390/ijms232416036 -
Molecules (Basel, Switzerland) Dec 2022Synthesis of '-Di-Boc-2H-isoindole-2-carboxamidine, the first representative of isoindoles containing guanidine functionality, was carried out. The cycloaddition...
Synthesis of '-Di-Boc-2H-isoindole-2-carboxamidine, the first representative of isoindoles containing guanidine functionality, was carried out. The cycloaddition reactivity of this new Diels-Alder heterodiene was studied and the title compound was employed as a cycloaddition delivery reagent for guanidine functionality. Higher reactivity was found in comparison with the corresponding pyrrole derivative. Substitution with fluorine or guanidine functionality does not change the reactivities of isoindoles, and these findings are in good accord with computational results.
Topics: Guanidine; Isoindoles; Guanidines; Indicators and Reagents; Cycloaddition Reaction
PubMed: 36558087
DOI: 10.3390/molecules27248954 -
ELife Apr 2024Metabolism and biological functions of the nitrogen-rich compound guanidine have long been neglected. The discovery of four classes of guanidine-sensing riboswitches and...
Metabolism and biological functions of the nitrogen-rich compound guanidine have long been neglected. The discovery of four classes of guanidine-sensing riboswitches and two pathways for guanidine degradation in bacteria hint at widespread sources of unconjugated guanidine in nature. So far, only three enzymes from a narrow range of bacteria and fungi have been shown to produce guanidine, with the ethylene-forming enzyme (EFE) as the most prominent example. Here, we show that a related class of Fe- and 2-oxoglutarate-dependent dioxygenases (2-ODD-C23) highly conserved among plants and algae catalyze the hydroxylation of homoarginine at the C6-position. Spontaneous decay of 6-hydroxyhomoarginine yields guanidine and 2-aminoadipate-6-semialdehyde. The latter can be reduced to pipecolate by pyrroline-5-carboxylate reductase but more likely is oxidized to aminoadipate by aldehyde dehydrogenase ALDH7B . Arabidopsis has three 2-ODD-C23 isoforms, among which Din11 is unusual because it also accepted arginine as substrate, which was not the case for the other 2-ODD-C23 isoforms from Arabidopsis or other plants. In contrast to EFE, none of the three Arabidopsis enzymes produced ethylene. Guanidine contents were typically between 10 and 20 nmol*(g fresh weight) in Arabidopsis but increased to 100 or 300 nmol*(g fresh weight) after homoarginine feeding or treatment with Din11-inducing methyljasmonate, respectively. In 2-ODD-C23 triple mutants, the guanidine content was strongly reduced, whereas it increased in overexpression plants. We discuss the implications of the finding of widespread guanidine-producing enzymes in photosynthetic eukaryotes as a so far underestimated branch of the bio-geochemical nitrogen cycle and propose possible functions of natural guanidine production.
Topics: Guanidine; Mixed Function Oxygenases; Homoarginine; Arabidopsis; Guanidines; Protein Isoforms; 2-Aminoadipic Acid
PubMed: 38619227
DOI: 10.7554/eLife.91458 -
Biochimica Et Biophysica Acta Oct 2010The pentein superfamily is a mechanistically diverse superfamily encompassing both noncatalytic proteins and enzymes that catalyze hydrolase, dihydrolase and... (Review)
Review
The pentein superfamily is a mechanistically diverse superfamily encompassing both noncatalytic proteins and enzymes that catalyze hydrolase, dihydrolase and amidinotransfer reactions on guanidine substrates. Despite generally low sequence identity, they possess a conserved structural fold and display common mechanistic themes in catalysis. The structurally characterized catalytic penteins possess a conserved core of residues that include a Cys, His and two polar, guanidine-binding residues. All known catalytic penteins use the core Cys to attack the substrate's guanidine moiety to form a covalent thiouronium adduct and all cleave one or more of the guanidine C--N bonds. The mechanistic information compiled to date supports the hypothesis that this superfamily may have evolved divergently from a catalytically promiscuous ancestor.
Topics: Animals; Catalysis; Enzymes; Guanidine; Humans; Models, Molecular; Multigene Family
PubMed: 20654741
DOI: 10.1016/j.bbapap.2010.07.016 -
Molecules (Basel, Switzerland) Dec 2022A series of benzyl, phenyl guanidine, and aminoguandine hydrazone derivatives was designed and in vitro antibacterial activities against two different bacterial strains...
A series of benzyl, phenyl guanidine, and aminoguandine hydrazone derivatives was designed and in vitro antibacterial activities against two different bacterial strains ( and ) were determined. Several compounds showed potent inhibitory activity against the bacterial strains evaluated, with minimal inhibitory concentration (MIC) values in the low µg/mL range. Of all guanidine derivatives, 3-[2-chloro-3-(trifluoromethyl)]-benzyloxy derivative showed the best potency with MICs of 0.5 µg/mL () and 1 µg/mL (), respectively. Several aminoguanidine hydrazone derivatives also showed good overall activity. Compounds , , and - displayed MICs of 4 µg/mL against both and . In the aminoguanidine hydrazone series, 3-(4-trifluoromethyl)-benzyloxy derivative showed the best potency against (MIC 1 µg/mL) but was far less active against (MIC 16 µg/mL). Compound and the -substituted derivative also showed promising results against two strains of methicillin-resistant (MRSA). These results provide new and potent structural leads for further antibiotic optimisation strategies.
Topics: Methicillin-Resistant Staphylococcus aureus; Staphylococcus aureus; Escherichia coli; Guanidine; Hydrazones; Anti-Infective Agents; Anti-Bacterial Agents; Guanidines; Microbial Sensitivity Tests
PubMed: 36615201
DOI: 10.3390/molecules28010005 -
Marine Drugs Apr 2016Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological... (Review)
Review
Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida marine sponges. In this review, we will explore the chemodiversity of tri- and pentacyclic guanidine alkaloids. NMR and MS data tools will also be provided, and an overview of the wide range of bioactivities of crambescidins and batzelladines derivatives will be given.
Topics: Alkaloids; Animals; Biological Factors; Guanidine; Humans; Porifera
PubMed: 27070629
DOI: 10.3390/md14040077